Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.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.Bibenzyls: Compounds with 1,2-diphenylethane. They are structurally like reduced STILBENES.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.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.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.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)Ancitabine: Congener of CYTARABINE that is metabolized to cytarabine and thereby maintains a more constant antineoplastic action.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.Gallium: A rare, metallic element designated by the symbol, Ga, atomic number 31, and atomic weight 69.72.Depsipeptides: Compounds consisting of chains of AMINO ACIDS alternating with CARBOXYLIC ACIDS via ester and amide linkages. They are commonly cyclized.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.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.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.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.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.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.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).Cell Line, Tumor: A cell line derived from cultured tumor cells.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.Sarcoma 180Molecular 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.Lactones: Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES.Leukemia L1210Antimetabolites, Antineoplastic: Antimetabolites that are useful in cancer chemotherapy.Daunorubicin: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.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.Drug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.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.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.Neoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.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.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.Stilbenes: Organic compounds that contain 1,2-diphenylethylene as a functional group.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.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.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)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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Lung Neoplasms: Tumors or cancer of the LUNG.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.Vincristine: An antitumor alkaloid isolated from VINCA ROSEA. (Merck, 11th ed.)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)Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.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.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Breast Neoplasms: Tumors or cancer of the human BREAST.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.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.Stereoisomerism: 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)Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.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)Cell Line: Established cell cultures that have the potential to propagate indefinitely.Kinetics: The rate dynamics in chemical or physical systems.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.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.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.Prostatic Neoplasms: Tumors or cancer of the PROSTATE.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.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).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.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.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.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.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.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).Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation.Olacaceae: A small plant family of the order Santalales, subclass Rosidae, class Magnoliopsida.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.Medical Secretaries: Individuals responsible for various duties pertaining to the medical office routine.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.LaunderingSulindac: 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.Dental Physiological Processes: Functions and activities of DENTITION as a whole.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.Equipment Contamination: The presence of an infectious agent on instruments, prostheses, or other inanimate articles.Amsacrine: An aminoacridine derivative that intercalates into DNA and is used as an antineoplastic agent.Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or CHEMICAL WARFARE AGENTS, from a person or object.Vanadium Compounds: Inorganic compounds that contain vanadium as an integral part of the molecule.Phlebitis: Inflammation of a vein, often a vein in the leg. Phlebitis associated with a blood clot is called (THROMBOPHLEBITIS).Nursing Staff, Hospital: Personnel who provide nursing service to patients in a hospital.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.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.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.ThiosemicarbazonesCarcinoma, 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.Personnel, Hospital: The individuals employed by the hospital.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.Drug Compounding: The preparation, mixing, and assembling of a drug. (From Remington, The Science and Practice of Pharmacy, 19th ed, p1814)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.Antineoplastic Protocols: Clinical protocols used to inhibit the growth or spread of NEOPLASMS.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.Pharmacies: Facilities for the preparation and dispensing of drugs.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)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)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.Drug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Farnesyltranstransferase: An enzyme that catalyzes the synthesis of geranylgeranyl diphosphate from trans, trans-farnesyl diphosphate and isopentenyl diphosphate.Oncology Service, Hospital: The hospital department responsible for the administration and provision of diagnostic and therapeutic services for the cancer patient.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.Drugs, Investigational: Drugs which have received FDA approval for human testing but have yet to be approved for commercial marketing. This includes drugs used for treatment while they still are undergoing clinical trials (Treatment IND). The main heading includes drugs under investigation in foreign countries.Isocoumarins: Compounds that differ from COUMARINS in having the positions of the ring and ketone oxygens reversed so the keto oxygen is at the 1-position of the molecule.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.Nurses: Professionals qualified by graduation from an accredited school of nursing and by passage of a national licensing examination to practice nursing. They provide services to patients requiring assistance in recovering or maintaining their physical or mental health.DioxolesSuramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.Hospitals: Institutions with an organized medical staff which provide medical care to patients.Alkaloids: Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.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.Topoisomerase I Inhibitors: Compounds that inhibit the activity of DNA TOPOISOMERASE I.Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.DNA Adducts: The products of chemical reactions that result in the addition of extraneous chemical groups to DNA.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.Anti-Inflammatory Agents, Non-Steroidal: Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.Nitrosourea CompoundsMice, Inbred BALB CPharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy.Lethal Dose 50: The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population.Pyrones: Keto-pyrans.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action 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.PyrazinesMetabolic Detoxication, Drug: Reduction of pharmacologic activity or toxicity of a drug or other foreign substance by a living system, usually by enzymatic action. It includes those metabolic transformations that make the substance more soluble for faster renal excretion.HT29 Cells: Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Hydrazones: Compounds of the general formula R:N.NR2, as resulting from the action of hydrazines with aldehydes or ketones. (Grant & Hackh's Chemical Dictionary, 5th ed)Sulfonamides: A group of compounds that contain the structure SO2NH2.DNA, Neoplasm: DNA present in neoplastic tissue.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.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.Mammary Neoplasms, Experimental: Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.Razoxane: An antimitotic agent with immunosuppressive properties.Phosphorylcholine: Calcium and magnesium salts used therapeutically in hepatobiliary dysfunction.Organoplatinum Compounds: Organic compounds which contain platinum as an integral part of the molecule.Octreotide: A potent, long-acting synthetic SOMATOSTATIN octapeptide analog that inhibits secretion of GROWTH HORMONE and is used to treat hormone-secreting tumors; DIABETES MELLITUS; HYPOTENSION, ORTHOSTATIC; HYPERINSULINISM; hypergastrinemia; and small bowel fistula.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.Lomustine: An alkylating agent of value against both hematologic malignancies and solid tumors.PiperazinesMitomycins: 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.Dehydroascorbic Acid: The reversibly oxidized form of ascorbic acid. It is the lactone of 2,3-DIKETOGULONIC ACID and has antiscorbutic activity in man on oral ingestion.Anthracyclines: Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine.Cancer Care Facilities: Institutions specializing in the care of cancer patients.

Tyrosine kinase inhibitor emodin suppresses growth of HER-2/neu-overexpressing breast cancer cells in athymic mice and sensitizes these cells to the inhibitory effect of paclitaxel. (1/4985)

Overexpression of the HER-2/neu proto-oncogene, which encodes the tyrosine kinase receptor p185neu, has been observed in tumors from breast cancer patients. We demonstrated previously that emodin, a tyrosine kinase inhibitor, suppresses tyrosine kinase activity in HER-2/neu-overexpressing breast cancer cells and preferentially represses transformation phenotypes of these cells in vitro. In the present study, we examined whether emodin can inhibit the growth of HER-2/neu-overexpressing tumors in mice and whether emodin can sensitize these tumors to paclitaxel, a commonly used chemotherapeutic agent for breast cancer patients. We found that emodin significantly inhibited tumor growth and prolonged survival in mice bearing HER-2/neu-overexpressing human breast cancer cells. Furthermore, the combination of emodin and paclitaxel synergistically inhibited the anchorage-dependent and -independent growth of HER-2/neu-overexpressing breast cancer cells in vitro and synergistically inhibited tumor growth and prolonged survival in athymic mice bearing s.c. xenografts of human tumor cells expressing high levels of p185neu. Both immunohistochemical staining and Western blot analysis showed that emodin decreases tyrosine phosphorylation of HER-2/neu in tumor tissue. Taken together, our results suggest that the tyrosine kinase activity of HER-2/neu is required for tumor growth and chemoresistance and that tyrosine kinase inhibitors such as emodin can inhibit the growth of HER-2/neu-overexpressing tumors in mice and also sensitize these tumors to paclitaxel. The results may have important implications in chemotherapy for HER-2/neu-overexpressing breast tumors.  (+info)

CLIP-170 highlights growing microtubule ends in vivo. (2/4985)

A chimera with the green fluorescent protein (GFP) has been constructed to visualize the dynamic properties of the endosome-microtubule linker protein CLIP170 (GFP-CLIP170). GFP-CLIP170 binds in stretches along a subset of microtubule ends. These fluorescent stretches appear to move with the growing tips of microtubules at 0.15-0.4 microm/s, comparable to microtubule elongation in vivo. Analysis of speckles along dynamic GFP-CLIP170 stretches suggests that CLIP170 treadmills on growing microtubule ends, rather than being continuously transported toward these ends. Drugs affecting microtubule dynamics rapidly inhibit movement of GFP-CLIP170 dashes. We propose that GFP-CLIP170 highlights growing microtubule ends by specifically recognizing the structure of a segment of newly polymerized tubulin.  (+info)

The topoisomerase-related function gene TRF4 affects cellular sensitivity to the antitumor agent camptothecin. (3/4985)

Camptothecin is an antitumor agent that kills cells by converting DNA topoisomerase I into a DNA-damaging poison. Although camptothecin derivatives are now being used to treat tumors in a variety of clinical protocols, the cellular factors that influence sensitivity to the drug are only beginning to be understood. We report here that two genes required for sister chromatid cohesion, TRF4 and MCD1/SCC1, are also required to repair camptothecin-mediated damage to DNA. The hypersensitivity to camptothecin in the trf4 mutant does not result from elevated expression of DNA topoisomerase I. We show that Trf4 is a nuclear protein whose expression is cell cycle-regulated at a post-transcriptional level. Suppression of camptothecin hypersensitivity in the trf4 mutant by gene overexpression resulted in the isolation of three genes: another member of the TRF4 gene family, TRF5, and two genes that may influence higher order chromosome structure, ZDS1 and ZDS2. We have isolated and sequenced two human TRF4 family members, hTRF4-1 and hTRF4-2. The hTRF4-1 gene maps to chromosome 5p15, a region of frequent copy number alteration in several tumor types. The evolutionary conservation of TRF4 suggests that it may also influence mammalian cell sensitivity to camptothecin.  (+info)

Fractionated administration of irinotecan and cisplatin for treatment of lung cancer: a phase I study. (4/4985)

A combination chemotherapy of irinotecan (CPT-11) and cisplatin (CDDP) has been reported to be active for lung cancer. In the previous trial, however, diarrhoea and leucopenia became the major obstacle for sufficient dose escalation of CPT-11 to improve the treatment outcome. We conducted a phase I study to investigate whether the fractionated administration of CDDP and CPT-11 at escalated dose was feasible and could improve the treatment outcome. Twenty-four previously untreated patients with unresectable non-small-cell lung cancer (NSCLC) or extensive disease of small-cell lung cancer (SCLC) were eligible. Both CDDP and CPT-11 were given on days 1 and 8, and repeated every 4 weeks. The dose of CDDP was fixed at 60 mg m(-2) and given by 1-h infusion before CPT-11 administration. The starting dose of CPT-11 was 40 mg m(-2), and the dose was escalated by an increase of 10 mg m(-2). The maximally tolerated dose of CPT-11 was determined as 60 mg m(-2) because grade 4 haematological or grade 3 or 4 non-haematological toxicities developed in six patients out of 11 patients evaluated. Diarrhoea became a dose-limiting toxicity. The objective response rates were 76% for NSCLC and 100% for SCLC. The recommended dose of CPT-11 and CDDP in a phase II study will be 50 mg m(-2) and 60 mg m(-2) respectively.  (+info)

A novel taxane with improved tolerability and therapeutic activity in a panel of human tumor xenografts. (5/4985)

Clinically available taxanes represent one of the most promising class of antitumor agents, despite several problems with their solubility and toxicity. In an attempt to improve the pharmacological profile of taxanes, a new series of analogues was synthesized from 14beta-hydroxy-10-deacetylbaccatin III and tested in a panel of human tumor cell lines. On the basis of the pattern of cytotoxicity and lack of cross-resistance in tumor cell lines expressing the typical multidrug-resistant phenotype, a compound (IDN5109) was selected for preclinical development. A comparative efficacy study of IDN5109 and paclitaxel was performed using a large panel of human tumor xenografts, characterized by intrinsic (seven tumors) or acquired (four tumors) resistance to cisplatin or doxorubicin, including four ovarian, one breast, one cervical, three lung, one colon, and one prostatic carcinoma. Drugs were delivered i.v. according to the same schedule (four times every 4th day). IDN5109 achieved a very high level of activity (percentage tumor weight inhibition >70%; log10 cell kill >1) in all but one of the tested tumors. Compared to paclitaxel, IDN5109 exhibited a significantly superior activity in six tumors (including the four tumors that were resistant to paclitaxel) and a comparable activity against the other five paclitaxel-responsive tumors. Additional advantages of IDN5109 over paclitaxel were also suggested by its toxicity profile. IDN5109 was not only less toxic (maximal tolerated doses were 90 and 54 mg/kg for IDN5109 and paclitaxel, respectively), but it also appeared to be endowed with a reduced neurotoxic potential and an improved profile of tolerability compared to the parent drug. Furthermore, the best antitumor efficacy was often already reached with doses lower than the maximal tolerated dose, suggesting an improved therapeutic index for the new drug. In conclusion, the results support the preclinical interest of IDN5109 in terms of the toxicity profile and of the efficacy with particular reference to the ability to overcome multiple mechanisms of drug resistance.  (+info)

Enhanced antitumor activity of 6-hydroxymethylacylfulvene in combination with irinotecan and 5-fluorouracil in the HT29 human colon tumor xenograft model. (6/4985)

6-Hydroxymethylacylfulvene (MGI-114) is a semisynthetic analogue of the toxin illudin S, a product of the Omphalotus mushroom. MGI-114 induces cytotoxicity in a variety of solid tumors in vivo, including the refractory HT29 human colon cancer xenograft. In this study, the potential application of MGI-114 in the treatment of colon cancer was further explored by evaluating the activity of MGI-114 in combination with irinotecan (CPT-11) and 5-fluorouracil (5FU). Groups of 9 nude mice bearing HT29 xenografts were treated with either single agent MGI-114, CPT-11, or 5FU, or MGI-114 in combination with CPT-11 or 5FU. MGI-114 was administered at doses of 3.5 and 7 mg/kg i.p. daily on days 1 through 5, and CPT-11 and 5FU were administered at doses of 50 and 100 mg/kg i.p. on days 1, 12, and 19. In the single agent studies, MGI-114, CPT-11, and 5FU all resulted in decreased final tumor weights compared with vehicle-treated controls (P<0.05), but only MGI-114 at 7 mg/kg produced partial responses. When MGI-114 at 3.5 mg/kg was combined with CPT-11, significant decrements in final tumor weights occurred compared with monotherapy with the same doses of MGI-114 and CPT-11 (P< or =0.001). Also, administration of the low-dose combination (MGI-114 at 35 mg/kg and CPT-11 at 50 mg/kg) resulted in final tumor weights similar to those achieved after administration of high-dose MGI-114 as a single agent. Moreover, the combination of MGI-114 and CPT-11 produced partial responses in nearly all of the animals, with some animals achieving complete responses. The outcome with the combination of MGI-114 and 5FU was less striking, with fewer partial responses and no complete responses. These results suggest enhanced activity when MGI-114 is combined with CPT-11, and clinical trials to further evaluate this combination regimen are planned.  (+info)

Cyclosporine inhibited calcium-mediated apoptosis of HL-60 cells. (7/4985)

AIM: To study the effects of cyclosporine (Cyc) on apoptosis of HL-60 cells. METHODS: Apoptotic cells induced by harringtonine (Har), camptothecin (Cam), or calcimycin (Cal), thapsigargin (Tha) were identified with DNA electrophoresis, morphology, and flow cytometry. Relative [Ca2+]i alteration of apoptotic HL-60 cells were determined with flow cytometry. RESULTS: Cal 1 mg.L-1 or Tha 0.5 mg.L-1 induced apoptosis of HL-60 cells. This effect was inhibited by nontoxic concentration of Cyc 1 mg.L-1. Cyc did not inhibit Har- or Cam-induced apoptosis of HL-60 cells. Both Cal and Tha increased intracellular calcium, whereas Har or Cam did not. CONCLUSION: Cyc inhibited apoptosis only induced by calcium increasement in HL-60 cells. The mechanism of apoptosis induced by Cal or Tha was different from that by Har or Cam.  (+info)

Quercetin induced apoptosis in human leukemia HL-60 cells. (8/4985)

AIM: To examine whether quercetin (Que) might induce apoptosis in human leukemia HL-60 cells. METHODS: DNA fragmentation was visualized by agarose gel electrophoresis. Inhibition of proliferation was measured with a colorimetric MTT-assay. The DNA degradation was determined using flow cytometry, and the microscopic changes were observed by an electron microscope. RESULTS: Que 15-120 mumol.L-1 elicited typical apoptosis morphological changes including condensed chromatin, nuclear fragmentation, and reduction in volume. DNA fragmentation and DNA degradation in a concentration-dependent manner in HL-60 cells. Que inhibited HL-60 cell proliferation. The values of IC50 and 95% confidence limits were 43 (30-61) mumol.L-1 after 48-h treatment with Que. CONCLUSION: Que induced apoptosis in HL-60 cells.  (+info)

*List of MeSH codes (D16)

... antineoplastic agents, hormonal MeSH D27.505.954.248.179 --- antineoplastic agents, phytogenic MeSH D27.505.954.248.589 --- ... antineoplastic MeSH D27.505.954.248.147 --- antimitotic agents MeSH D27.505.954.248.150 --- antineoplastic agents, alkylating ... File "2006 MeSH Trees".) MeSH D27.505.519.124 --- alkylating agents MeSH D27.505.519.124.035 --- antineoplastic agents, ... lipotropic agents MeSH D27.505.954.248 --- antineoplastic agents MeSH D27.505.954.248.025 --- angiogenesis inhibitors MeSH ...
RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab and ramucirumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab and ramucirumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. It is not yet know whether giving cetuximab and irinotecan hydrochloride together is more effective with or without ramucirumab in treating colorectal cancer.. PURPOSE: This randomized phase II trial is studying the side effects and how well giving cetuximab and irinotecan hydrochloride with or without ramucirumab work in treating patients with advanced colorectal cancer with progressive disease after treatment with bevacizumab-containing chemotherapy. ...
PRIMARY OBJECTIVES:. l. To compare the overall survival (OS) of subjects receiving the combination of temozolomide and irinotecan with that of subjects receiving temozolomide, irinotecan (irinotecan hydrochloride), and bevacizumab for recurrent medulloblastoma (MB)/primitive neuroectodermal tumor (PNET) of childhood.. SECONDARY OBJECTIVES:. I. To assess the response rate for each treatment arm amongst patients who are enrolled with measurable disease.. II. To determine event-free survival (EFS) for each patient compared across regimens.. OUTLINE: Patients are randomized to 1 of 2 treatment arms.. ARM I: Patients receive temozolomide orally (PO) and irinotecan hydrochloride IV over 90 minutes on days 1-5.. ARM II: Patients receive temozolomide PO and irinotecan hydrochloride IV as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15.. In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.. After completion of ...
Irinotecan Hydrochloride Trihydrate for Injection by Sandoz Canada Inc.: Irinotecan belongs to the group of cancer-fighting medications known as antineoplastics. It kills cancer cells by interfering with the genetic material DNA, which is necessary for their growth and reproduction. Irinotecan is usually used in combination with other medications to treat colon or rectal cancer.
Fourteen RCTs were included in the review. These included 1 RCT (429 patients) of docetaxel as first-line treatment for breast cancer, 4 RCTs (1,545 patients) of paclitaxel as first-line treatment for breast cancer, 4 RCTs (1,092 patients) of docetaxel as second-line treatment for breast cancer, and 1 RCT (81 patients) of paclitaxel as second-line treatment for breast cancer. There were also 4 RCTs (3,746 patients) of paclitaxel as first-line treatment for ovarian cancer.. Paclitaxel for first-line treatment for breast cancer (4 RCTs):. Three trials looked at single-agent paclitaxel. The median progression-free survival in the paclitaxel arm ranged from 4 to 5.9 months; in no trial was this greater than the control arm. In one trial, the anthracycline group had significantly longer progression-free survival than single-agent paclitaxel (7.5 versus 4.0 months, p=0.0001). The median length of overall survival in the paclitaxel arm ranged from 17.3 to 22.2 months; in no trial was this significantly ...
Find a comprehensive guide to possible side effects including common and rare side effects when taking Camptosar Injection (Irinotecan Hydrochloride) for healthcare professionals and consumers.
BioAssay record AID 95653 submitted by ChEMBL: In vitro cytotoxic activity was determined against epidermoid carcinoma of the nasopharynx (KB) cell line.
Progression free survival of patients treated with Tumor Treating Fields plus weekly paclitaxel was more than double that of weekly paclitaxel-treated
In the intent-to-treat analysis of the pooled data across all three studies, 193 of the 304 patients began therapy at the recommended starting dose of 125 mg/m2. Among these 193 patients, 2 complete and 27 partial responses were observed, for an overall response rate of 15.0% (95% Confidence Interval [CI], 10.0% to 20.1%) at this starting dose. A considerably lower response rate was seen with a starting dose of 100 mg/m2. The majority of responses were observed within the first two cycles of therapy, but responses did occur in later cycles of treatment (one response was observed after the eighth cycle). The median response duration for patients beginning therapy at 125 mg/m2 was 5.8 months (range, 2.6 to 15.1 months). Of the 304 patients treated in the three studies, response rates to Irinotecan were similar in males and females and among patients older and younger than 65 years. Rates were also similar in patients with cancer of the colon or cancer of the rectum and in patients with single and ...
The administration of paclitaxel to patients with renal insufficiency has been reported previously in five cases and in all, patients were on (long-term) hemodialysis (Schilder et al., 1994;Fazeny et al., 1995; Balat et al., 1996; Conley et al., 1997; Woo et al., 1999). Although paclitaxel pharmacokinetics was determined in some of these patients, the lack of fecal and urinary data precluded a complete analysis of paclitaxel disposition. In contrast to these previous investigations, we evaluated paclitaxel plasma pharmacokinetics during six sequential evaluated courses. Our patient exhibited a quantitatively distinct kinetic profile of paclitaxel, with paclitaxel AUC values and disposition half-lives in plasma approximately 1.5- to 2-fold higher as compared with those reported in patients with normal renal function (Rowinsky, 1995; Gianni et al., 1995). This high paclitaxel AUC value, which was sustained over the six consecutive courses, justifies a dose reduction of paclitaxel in patients with ...
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Two major side-effects of paclitaxel therapy are frequent hypersensitivity reactions and neuropathy. Standard paclitaxel contains Cremophor EL as a solvent, thus requiring premedication with high doses of antihistamines and corticosteroids, as well as prolonged infusion times. Albumin-bound or nab-paclitaxel was developed to overcome such limitations, and also to ensure more convenient drug administration and improve toxicity profiles.
E1A is associated with many antitumor activities and has been tested in multiple clinical trials. Studies have shown that, although E1A gene therapy is safe and well tolerated, the tumor response to it is only modest (14-16). However, E1A has been shown to induce sensitization to apoptosis induced by different categories of anticancer drugs; therefore, one improvement that might render E1A more useful as an anticancer therapy is the combination of E1A gene therapy with conventional chemotherapy. Paclitaxel is a front-line chemotherapeutic agent for the treatment of human breast and ovarian cancer. One of the mechanisms that paclitaxel uses to induce apoptosis in cancer cells is through increasing Bim (proapoptotic BH3-only protein) expression by activated FOXO3a activity (34). In the present study, we found that E1A can stabilize FOXO3a, thus sensitizing MDA-MB-231 breast cancer cells to paclitaxel-induced apoptosis both in vitro and in vivo. This result provides a molecular mechanism for ...
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New research shows how the side effects of the common chemotherapy drug paclitaxel may cause cancer to spread from the breast to the lungs.
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Learn more about SYNRIBO (omacetaxine mepesuccinate) for Injection, for subcutaneous use, including indication, treatment, safety information, and MOA.
Paclitaxel is mainly associated with symptoms and indications-The International Classification of Diseases (ICD)- L01CD01-Paclitaxel ...
Paclitaxel released from a self-assembling supramolecule in the presence of the MMP-2 enzyme. Various complexes of peptides and paclitaxel (paclitaxel 100 μg)
Find out about the science and chemistry of Docetaxel (Taxotere), see colourful images of Docetaxel and explore interactive 3D molecules of Docetaxel
... is a medicine prescribed for treating lung cancer, breast cancer, and ovarian cancer. This eMedTV resource describes paclitaxel uses in more detail, explains how the medication works, and offers general dosing information.
... is a medicine prescribed for treating lung cancer, breast cancer, and ovarian cancer. This eMedTV resource describes paclitaxel uses in more detail, explains how the medication works, and offers general dosing information.
Paclitaxel Delta Farma is a medicine available in a number of countries worldwide. A list of US medications equivalent to Paclitaxel Delta Farma is available on the Drugs.com website.
Paclitaxel Techsphere is a medicine available in a number of countries worldwide. A list of US medications equivalent to Paclitaxel Techsphere is available on the Drugs.com website.
Irinotecan is a chemotherapy drug that is given as a treatment for some types of cancer. It is most commonly used to treat bowel cancer...
Page contains details about example of paclitaxel comprising stable nanocomposition . It has composition images, properties, Characterization methods, synthesis, applications and reference articles : nano.nature.com
Page contains details about example of docetaxel comprising stable nanocomposition . It has composition images, properties, Characterization methods, synthesis, applications and reference articles : nano.nature.com
BACKGROUND: Less than 50% of ovarian cancers respond to paclitaxel. Effective strategies are needed to enhance paclitaxel sensitivity. METHODS: A library of silencing RNAs (siRNAs) was used to identify kinases that regulate paclitaxel sensitivity in human ovarian cancer SKOv3 cells. The effect of dasatinib, an inhibitor of Src and Abl kinases, on paclitaxel sensitivity was measured in ovarian cancer cells and HEY xenografts. The roles of p27(Kip1), Bcl-2, and Cdk1 in apoptosis induced by dasatinib and paclitaxel were assessed using a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, siRNA knockdown of gene expression, transfection with Bcl-2 and Cdk1 expression vectors, and flow cytometry. All statistical tests were two-sided. RESULTS: Src family and Abl kinases were identified as modulators of paclitaxel sensitivity in SKOv3 cells. The siRNA knockdown of Src, Fyn, or Abl1 enhanced paclitaxel-mediated growth inhibition in ovarian cancer cells compared with a control
In this study, evidence has been collected that supports the notion that paclitaxel may exert its toxicity via elevation of intracellular O2−, H2O2, and NO levels. This theory is confirmed by our data showing that (a) paclitaxel induced the production of O2−, H2O2 and NO; (b) paclitaxel induced oxidative DNA damage; (c) agents that decreased H2O2 and NO production suppressed paclitaxel-induced DNA damage, G2-M arrest, apoptosis, and cell growth inhibition; (d) inhibition of SOD or glutamylcysteine synthase increased paclitaxel-induced apoptosis; (e) cell lines with higher total antioxidant capacity were more resistant to paclitaxel cytotoxicity; and (f) agents that decreased clonogenic survival in paclitaxel-treated cells also decreased cellular total antioxidant capacity. Thus, paclitaxel chemoresistance correlates very well to intracellular antioxidant capacity.. Kong et al. ( 27) speculated that many chemotherapeutic agents exert their toxic effects on cancer cells by producing free ...
Paclitaxel, a chemotherapy drug frequently used to treat a range of cancers, is considered a microtubule inhibitor that arrests tumor cells in mitosis, but concentrations that have been used in cell culture to characterize the mechanism of action may be much higher than intratumoral concentrations. To determine clinically relevant paclitaxel concentrations in breast cancer, Zasadil and colleagues enrolled 6 patients in a clinical trial in which intratumoral paclitaxel levels and mitotic status were evaluated before and 20 hours after infusion with neoadjuvant paclitaxel, and tumor response was evaluated after 3 additional standard cycles of paclitaxel therapy. Interestingly, in 5 evaluable patients, mitotic arrest did not correlate with tumor regression. Concentrations of paclitaxel deemed clinically relevant based on levels in patient plasma and tumor samples 20 hours after initial infusion remained sufficient in inducing cell death in breast cancer cell lines but did so by increasing the ...
The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the individual clearance of unbound paclitaxel was estimated from total plasma paclitaxel and Cremophor EL. The geometric mean of clearance was 385 l h(-1) (range 176-726 l h(-1)). Carriers of CYP2C8*3 had 11% lower clearance than non-carriers, P = 0.03. This has not been shown before in similar studies; the explanation is probably the advantage of using both unbound paclitaxel clearance and a population of patients of same gender. No significant association was found for the ABCB1 variants C1236T, G2677T/A and C3435T. Secondarily, other candidate single-nucleotide polymorphisms were explored with possible associations found for CYP2C8*4 (P = 0.04) and ABCC1 g.7356253C andgt; G (P = 0.04).. ...
DESCRIPTION (provided by applicant): Inhibitor of differentiation (Id) genes and proteins play a significant role in tumor biology, and an anti-Id therapy in combination with a taxanes, a widely prescribed class of cytotoxic (paclitaxel/docetaxel, docetaxel or protein-bound paclitaxel) to treat cancer, is hypothesized to significantly improve the efficacy of the taxane without compromising safety while also providing additional anti-cancer activity. An effective Id1 inhibitor would potentially improve the efficacy of the taxanes by three distinct mechanisms: (i) preventing endothelial repair and thereby promoting the intrinsic anti-angiogenic effect of paclitaxel/docetaxel, (ii) lowering the anti-apoptotic environment of the tumor making it more susceptible to the cytotoxicity of paclitaxel/docetaxel and (iii) augmenting the cytotoxicity of paclitaxel/docetaxel by a direct anti-cancer effect. The goal of this proposal is to provide data to justify formal preclinical development and initial ...
The paclitaxel vehicle CrEL has been shown to influence the toxicity, pharmacokinetics, and antitumor activity of paclitaxel (2, 3, 4, 5 , 6, 7, 8 , 10, 11, 12, 13) . With regard to paclitaxel-induced HSR, CrEL is probably responsible, because other drugs formulated with it produce similar reactions, and CrEL-free paclitaxel does not cause HSR. Likewise, a growing body of evidence shows that CrEL itself is closely related with peripheral neuropathy, one of the main side effects reported for paclitaxel chemotherapy (28, 29, 30) . The CrEL concentrations achieved by therapeutic doses of paclitaxel have been shown to produce axonal swelling, vesicular degeneration, and demyelination in vivo (31) . Similarly, peripheral neuropathy is more augmented in short infusion because CrEL clearance increases by extending the infusion duration from 3 to 24 h (32) . Besides these issues, CrEL-formulated vehicle is associated with pharmacokinetic paclitaxel alterations. CrEL has been shown to cause nonlinear ...
Transposase activity was thought to be extinct in humans because DNA movement can be deleterious in higher organisms, resulting in genomic instability and perha...
This study was performed to explore the influence of alternate sequences of CPT-11 and CDDP on the observed side effects and pharmacokinetic behavior of both drugs. Using a randomized cross-over design for the administration sequence, no substantial differences in any toxicity were observed between the two treatment schedules. The pharmacokinetics of the lactone form of CPT-11 revealed a substantial degree of interpatient variability, in line with previous observations (17) . In addition, the observed kinetic parameters of CPT-11 were similar to single agent data (18) , indicating no apparent interaction between CDDP and CPT-11. The sequence of drug administration had also no influence on the pharmacokinetics of CPT-11 and its metabolites SN-38 and SN-38G and the CYP450 3A4-mediated metabolites APC and NPC at the dose levels administered. This contrasts the reduction of topotecan clearance observed previously in patients after CDDP administration (5) . Our findings, however, are consistent with ...
Paclitaxel for Injection by Hospira Healthcare Corporation: Paclitaxel belongs to the group of cancer-fighting medications known as antineoplastics. Paclitaxel works by slowing or stopping the growth of cancer cells in your body. Paclitaxel is used alone or in combination with other cancer medications to treat cancers of the ovary, breast, or lung. It may also be used to treat another form of cancer called Kaposis sarcoma.
Tomorrow will be 5 weeks since my last infusion.. During my 8-week course of the dose-dense A/C, I gained an additional 14 pounds, on top of my already 50 pounds of excess baggage. That was in spite of feeling so much like crap that I rarely ate. After two weeks off from chemo, I noticed I was losing almost a pound of weight per day, so that by the time I started the weekly paclitaxel infusions, I was back to my starting weight.. Then the scale crept up, up, up, again, until I was an additional 27 pounds. I didnt worry much about it. I thought it would start peeling off again when I was through with the paclitaxel. I couldnt wear my wedding ring, and I cant wear most of my clothes, but hey! Its temporary, right? Hmm. A two week break from paclitaxel, and no downward movement on the scale. I dont think I can blame all this weight gain on the steroid any more, and I said as much to my chemo nurse when I went back on the paclitaxel.. However, today, despite not having changed a thing, my ...
Taxol (Paclitaxel) chemotherapy side effects, how its given, how it works, precaution and self care tips for treatment of multiple cancers
... - description, side Effects of paclitaxel protein-bound, dosage (paclitaxel protein-bound), proper use of paclitaxel protein-bound. Drugs review.
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This trial compared the efficacy, pharmacokinetics, pharmacodynamics and tolerability of paclitaxel alone and in combination with LCL 161 [Novartis] in patients
NIHEI Yukio , SUZUKI Manabu , OKANO Akira , TSUJI Takashi , AKIYAMA Yukio , TSURUO Takashi , SAITO Sachiko , HORI Katsuyoshi , SATO Yasufumi Japanese journal of cancer research : gann 90(12), 1387-1396, 1999-12-30 医中誌Web 参考文献25件 被引用文献4件 ...
Preclinical pharmacokinetic models capable of predicting concentrations/exposure in vivo under different dosing schema can provide an invaluable tool for the rational design of clinical dosing protocols. The overall goals of the studies described herein were to design and evaluate the use of rational dosing protocols for vandetanib, docetaxel, and combinations of the two using pharmacokinetically directed dosing protocols that were reflective of exposures attainable in humans and that target antitumor and antiangiogenic responses. We utilized a PBPK model for docetaxel to develop dosing protocols that would allow us to examine the effects of standard docetaxel treatment versus a metronomic or antiangiogenic schedule of docetaxel. Pharmacokinetic data on vandetanib was used to determine a steady-state dose level that was reflective of human vandetanib exposure (32).. Preclinical testing is an integral part of the development of new therapeutics and new therapeutic strategies. With increasing ...
Paclitaxel drug is used for treating various types of cancers like breast cancer, ovarian cancer, lung cancer and certain types of skin cancers.
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Our results demonstrate an interaction between lovastatin and paclitaxel in several cellular processes. In both the K562 and HL-60 cell lines, lovastatin was found to enhance paclitaxel-induced cytotoxicity in a synergistic manner (Fig. 1 and 2). In addition, lovastatin enhanced paclitaxel-induced G2-M arrest in both cell lines and paclitaxel-induced apoptosis in the HL-60 cells (Fig. 3-5). These interactions were not attributable to an effect by lovastatin on cellular paclitaxel levels (Fig. 6) or to a general effect by paclitaxel on isoprenylated proteins (Fig. 7). However, we found evidence to suggest that alterations in the expression of the isoprenylated centromere-associated protein mitosin might be involved (Fig. 8 and 9).. Because of a report that indicated that paclitaxel could alter protein isoprenylation (26), we investigated the effects of lovastatin and/or paclitaxel treatment on several isoprenylated proteins. Importantly, we found no evidence to suggest that paclitaxel alters ...
TY - JOUR. T1 - Design, synthesis and potent cytotoxic activity of novel 7-(N-[(substituted-sulfonyl)piperazinyl]-methyl)-camptothecin derivatives. AU - Zhu,Gao Xiang. AU - Cheng,Pi Le. AU - Goto,Masuo. AU - Zhang,Na. AU - Morris-Natschke,Susan L.. AU - Hsieh,Kan Yen. AU - Yang,Guan Zhou. AU - Yang,Qian Ru. AU - Liu,Ying Qian. AU - Chen,Hai Le. AU - Zhang,Xiao Shuai. AU - Lee,Kuo Hsiung. PY - 2017. Y1 - 2017. N2 - In an effort to discover potent camptothecin-derived antitumor agents, novel camptothecin analogues with sulfonylpiperazinyl motifs at position-7 were designed and synthesized. They were evaluated for in vitro cytotoxicity with the sulforhodamine-B (SRB) method in five types of human tumor cell lines, A-549, MDA-MB-231, KB, KB-VIN and MCF-7. With IC50 values in the low μM to nM level, most of the new analogues showed greater cytotoxicity activity than the reference compounds irinotecan and topotecan. Furthermore, compounds 12l (IC50, 1.2 nM) and 12k (IC50, 20.2 nM) displayed the ...
Vincent L,Kermani P,Young LM,Cheng J,Zhang F,Shido K,Lam G,Bompais-Vincent H,Zhu Z,Hicklin DJ,Bohlen P,Chaplin DJ, et al. Combretastatin A4 phosphate induces rapid regression of tumor neovessels and growth through interference with vascular endothelial-cadherin signaling. J Clin Invest 2005; 115: 2992-3006 ...
This study will evaluate the clinical efficacy of combining Gleevec (imatinib mesylate), a PDGFR antagonist, with front-line, single-agent paclitaxel in
BACKGROUND: The identification of new therapies for high-risk (HR) hepatoblastoma is challenging. Childrens Oncology Group study AHEP0731 included a HR stratum to explore the efficacy of novel agents. Herein, the authors report the response rate to the combination of vincristine (V) and irinotecan (I) and the outcome of patients with high-risk hepatoblastoma. METHODS: Patients with newly diagnosed metastatic hepatoblastoma or those with a serum alpha-fetoprotein (AFP) level /mL were eligible. Patients received 2 cycles of V at a dose of 1.5 mg/m2 /day intravenously on days 1 and 8 and I at a dose of 50 mg/m2 /day intravenously on days 1 to 5. Patients were defined as responders if they had either a 30% decrease in tumor burden according to Response Evaluation Criteria In Solid Tumors (RECIST) or a 90% ( | 1 log10 ) decline in their AFP level. Responders were to receive 2 additional cycles of VI intermixed with 6 cycles of the combination of cisplatin, doxorubicin, 5-fluorouracil, and vincristine (C5VD)
I have performed several retrospective analyses of clinical trial datasets to discover pharmacogenetic, pharmacokinetic, and pharmacometabolomic predictors of paclitaxel-induced peripheral neuropathy and am currently collecting and analyzing larger cooperative group clinical trial cohorts to validate these findings. One ongoing project that I am particularly excited is using our previously published neuropathy prediction model, which includes paclitaxel pharmacokinetics and dosing, and attempting to introduce genetics to explain residual variability in the "neuropathy sensitivity" phenotype. I also have ongoing work in the pharmacogenetics of hormonal treatment in breast cancer. I am currently leading a meta-analysis of all patient cohorts that have tamoxifen pharmacokinetic data and CYP2D6 genetic data to generate an endoxifen prediction algorithm and empirically derive estimates of the percentage activity of individual CYP2D6 alleles. I hope that this project will improve the accuracy of ...
Taxotere is a chemotherapy drug used in the treatment of most cancers especially breast cancer. The objective of most chemotherapy drugs is to eradicate or slow down the growth of cancer cells without the risk of permanent side effects. Taxotere is associated with a wide range of side effects but one such consequence has been a subject of defective drug lawsuits against Sanofi Aventis, the manufacturer of Taxotere.. In a survey involving cancer patients, taxotere caused bone pain and muscle aches. Some claim that their arms and legs ache while others feel pain in their neck, back, and shoulder. Taxotere is also associated with neuropathy resulting to numbness and a tingy feeling in the feet and hands. It may also cause diarrhea, stomatitis, thinning of nails, and nail hyperpigmentation. The side effects of taxotere are individual and dosage dependent.. One of the most controversial side effects of taxotere that has put its manufacturer Sanofi Aventis in hot water is permanent alopecia. Although ...
Today, Biolyse Pharma is the industry leader in the research and development of injectable Paclitaxel products for use in cancer treatments.. Since Biolyse researchers first discovered that Paclitaxel could be produced from Taxus canadensis the company has gained fourteen years of valuable experience with the product. In September of 1994, Biolyse obtained authorization from the Federal Health Protection Branch (HPB) to administer its Paclitaxel for Injection, to patients under a clinical trial program.. Paclitaxel is a chemotherapeutic agent that is currently prescribed worldwide to treat the most aggressive forms of ovarian, lung and breast cancer, as well as AIDS related Kaposis sarcoma. Paclitaxel belongs to the chemical group known as taxanes, a family of molecules found in various natural sources. Paclitaxel is considered by the scientific and medical community as a first line of defense in the treatment of cancer. In 1992, both the American and Canadian National Cancer Institutes ...
An overview of why real-world data are pertinent to the safety assessment of paclitaxel-coated devices, with separate summaries of the projects investigating the late mortality signal via real-world data analyses.
Paclitaxel is a cancer medication that interferes with the growth and spread of cancer cells in the body. Paclitaxel is used to treat breast cancer, ovarian cancer, and lung cancer. It is also used to treat AIDS-related Kaposis sarcoma. Paclitaxel may also be used for purposes not listed in this medication guide.
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RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the
I have been testing the searches based on one of my adopted molecules, paclitaxel, sometimes referred to as Taxol.. Searching on paclitaxel without JBC and PNAS gives a total of 427 articles in 11 seconds.. Searching on Taxol without JBC and PNAS gives a total of 270 articles in 5 seconds.. Searching on paclitaxel with JBC and PNAS gives a total of 745 articles in 26 seconds.. Searching on Taxol with JBC and PNAS gives a total of 1192 articles in 35 seconds.. Clearly adding JBC and PNAS is giving a lot more hits on both names with over a 4x increase for Taxol hits. Clearly the number of hits is highly dependent on the name used to perform the searching. Now, when we integrate the chemical structure searching via linked identifiers this dependency should be dramatically reduced. This work is in development.. ...
Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using this medicine, tell your doctor right away. Omacetaxine can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:. ...
In a 1968 study, lapachol demonstrated highly significant activity against cancerous tumors in rats.39 Then in 1974, the NCI reported that Phase I clinical trials failed to produce a therapeutic effect with lapachol without side effects and discontinued further cancer research.40 In a small study in 1980 with nine patients with various cancers (liver, kidney, breast, prostate and cervix), pure lapachol demonstrated an ability to shrink tumors and reduce feeling of pain caused by these tumors and achieved complete remissions in three of the patients.41 It is believed that the antitumor activity of lapachol may be due to its interaction with nucleic acids. Additionally it has been proposed that interaction of the naphthoquinone moiety between base pairs of the DNA helix occurs with subsequent inhibition of DNA replication and RNA synthesis.42 Although lapachol has some beneficial effects, it is by no means a perfect anticancer drug. Despite the lack of significant toxicity even in large oral dose ...
Subjects will be randomized in a 1:1 ratio to receive CriPec docetaxel in cycle 1 and Taxotere in cycle 2 (Arm A) or Taxotere in cycle 1 and CriPec docetaxel in cycle 2 (Arm B). Both CriPec docetaxel and Taxotere will be administered at a dose of 75 mg/m2 (4-weekly, Q4W) and Taxotere at a dose of 75mg/m2 (3-weekly, Q3W). After completion of cycle 2, a radiographic evaluation will take place and the patients will go off study. Subjects without evidence of disease progression or drug related toxicity can continue treatment with Taxotere (75mg/m2, Q3W) according to local standard guidelines for Taxotere treatment until disease progression or unacceptable toxicity occurs ...
BioAssay record AID 332306 submitted by ChEMBL: Inhibition of etoposide-induced caspase 3 induction in human U937 cells after 7 hrs.
May 20, 2008. Taxotere ® Generic Name: Docetaxel Link to Scientific American Article from 1996, discussing Taxoids (this is a PDF file). Drug Type: Taxotere is an anti-cancer (antineoplastic or cytotoxic) chemotherapy drug. Taxotere is classified as a plant alkaloid, a taxane and an antimicrotubule agent. (For more detail, see How Taxotere Works section below).…
COA of Paclitaxel contains the actual results obtained from testing performed as part of quality control. View our Paclitaxel specific physical and chemical properties, and analytical data.
Antineoplastic agents frequently disrupt replication at the cellular level by obstructing the synthesis of new genetic material or by causing irreversible damage to the DNA itself. While this affects both normal and malignant cells, normal cells have a greater ability to repair minor damage and continue living. The increased weakness of malignant cells is exploited to achieve the therapeutic effects seen with the administration of antineoplastic agents.1
Docetaxel is a chemotherapy drug that is used in the treatment of several types of cancer. Chemotherapy treatments are also referred to as cytotoxic drugs, which means they are toxic and damaging to cells. Although these drugs are used to kill cancerous cells, they can also kill off healthy cells in the body.
My oncologist switched me this week to taxotere because the numbness in my fingers wasnt going away. I didnt have an immediate allergic reaction like I did with taxol, although I had some insomnia the first night (Tuesday night) and today I overslept, probably because of the rain (It has been rainy here for weeks,…
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Velban belongs to the group of medicines known as antineoplastic agents. It is used to treat certain kinds of cancer, including lymphoma and cancer of the breast or testicles,...
TY - JOUR. T1 - UNC-45A is a novel microtubule-associated protein and regulator of paclitaxel sensitivity in ovarian cancer cells. AU - Mooneyham, Ashley. AU - Iizuka, Yoshie. AU - Yang, Qing. AU - Coombes, Courtney. AU - McClellan, Mark. AU - Shridhar, Vijayalakshmi. AU - Emmings, Edith. AU - Shetty, Mihir. AU - Chen, Liqiang. AU - Ai, Teng. AU - Meints, Joyce. AU - Lee, Michael K.. AU - Gardner, Melissa. AU - Bazzaro, Martina. PY - 2019/2/1. Y1 - 2019/2/1. N2 - UNC-45A, a highly conserved member of the UCS (UNC45A/CRO1/SHE4P) protein family of cochaperones, plays an important role in regulating cytoskeletal-associated functions in invertebrates and mammalian cells, including cytokinesis, exocytosis, cell motility, and neuronal development. Here, for the first time, UNC-45A is demonstrated to function as a mitotic spindle-associated protein that destabilizes microtubules (MT) activity. Using in vitro biophysical reconstitution and total internal reflection fluorescence microscopy analysis, we ...
387485961 - EP 0943620 A3 2001-02-07 - Betulinic acid derivatives for inhibiting cancer growth - [origin: EP0943620A2] The invention relates to use of betulinic acid and/or its derivatives for treating, inhibiting, and/or preventing tumors or cancer growth more particularly, to treating leukemia, lymphomas, lung, prostate and ovarian cancer. This invention also relates to novel betulinic acid derivatives and a composition containing betulinic acid derivatives with or without betulinic acid. IMAGE [origin: EP0943620A2] The invention relates to use of betulinic acid and/or its derivatives for treating, inhibiting, and/or preventing tumors or cancer growth more particularly, to treating leukemia, lymphomas, lung, prostate and ovarian cancer. This invention also relates to novel betulinic acid derivatives and a composition containing betulinic acid derivatives with or without betulinic acid. IMAGE
Zybrestat (combretastatin A4 phosphate) is a prodrug that is converted to combretastatin inside the endothelial cells that line blood vessels. Combretastatin has a dual-mode of action, targeting both VE-cadherin, a junction protein that is important for endothelial cell survival, and the associated beta-catenin/AKT signalling pathway.. Once activated within the endothelial cell, it causes rapid collapse and necrosis of the tumours vascular structure.. As a reversible tubulin depolymerizing agent, combretastatin also causes tumour-associated endothelial cells to change from a flat to a round shape. This has the effect of plugging the blood vessels so depriving the tumour of the oxygen and nutrients it needs to survive.. Because the endothelial cells of tumours are immature they are much more sensitive to the effects of combretastatin than the endothelial cells of normal tissue.. ...
Background The main toxicity of irinotecan in advanced colorectal cancer (CRC) is delayed diarrhoea. Intestinal SN-38, released by deconjugation of the parent glucuronide excreted into the bile or produced in situ by intestinal carboxylesterase, is toxic to the intestinal epithelium. The canalicular transport of irinotecan and SN-38G is mediated by ABCC2 (MRP2) and ABCB1 (MDR1) which are both inhibited by ciclosporin. We tested whether irinotecan and ciclosporin was non-inferior for anti-cancer efficacy and superior for toxicity compared with single-agent irinotecan. Methods Six hundred and seventy-two patients with advanced, measurable CRC following prior fluoropyrimidine- containing chemotherapy were randomised to either irinotecan 3-weekly 350 mg/m 2 (or 300 mg/m 2 if age | 70 or performance status (PS) = 2) or 3-weekly irinotecan at 140 mg/m 2 (120 mg/m 2 if age | 70 or PS = 2) with ciclosporin 3 mg/kg t.d.s. for three days by mouth starting on the morning before irinotecan. The primary end
OXi-4503 is the diphosphate prodrug of the stilbenoid combretastatin A1, originally isolated from the plant Combretum caffrum, with vascular-disrupting and antineoplastic activities. Upon administration, combretastatin A1 diphosphate (CA1P) is dephosphorylated to the active metabolite combretastatin A1 (CA1), which promotes rapid microtubule depolymerization; endothelial cell mitotic arrest and apoptosis, destruction of the tumor vasculature, disruption of tumor blood flow and tumor cell necrosis may ensue.
Paclitaxel is used as a single agent, and in combination with other drugs, as a standard of care in the treatment of squamous cell carcinoma of the head and neck (SCCHN). However, the use of paclitaxe
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Nanoparticle albumin-bound (nab)-paclitaxel, an albumin-bound-stabilised paclitaxel formulation, has recently demonstrated significant improvements in median survival of patients with metastatic PDA when combined with gemcitabine.18 Since this drug combination represents the first therapeutic regimen that significantly extends survival of advanced stage PDA patients and is accompanied by an acceptable toxicity profile, nab-paclitaxel and gemcitabine will likely become the new standard of care chemotherapy and will shortly be implemented in national and international PDA treatment guidelines. Apart from the striking antitumour effect of nab-paclitaxel alone in KPC tumours, our group previously discovered a potential synergistic drug-drug interaction of gemcitabine and nab-paclitaxel due to ROS-mediated degradation of cytidine deaminase that resulted in higher levels of activated intratumoural gemcitabine metabolites.19 However, the limited availability of patient tissue and the lack of murine ...
Compositions and Methods of Use of Immunotoxins Comprising Ranpirnase (Rap) Show Potent Cytotoxic Activity - diagram, schematic, and image 69 ...
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The goal of this clinical research study is to learn if omacetaxine given with cytarabine can help to control the disease in patients with AML or high-risk MDS. The safety of the study drugs will also be studied.
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The relatively recent introduction of a new class of chemotherapeutic agents--the taxoids--has raised hope of improved survival for patients with advanced or metastatic cancer. Following encouraging preclinical results of taxoid combinations, this phase I, nonrandomized trial was designed to evaluate a 1-hour intravenous infusion of docetaxel (Taxotere) on day 1 combined with fluorouracil (5-FU) as a daily intravenous bolus for 5 consecutive days. 1
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A multi-university research team led by Virginia Tech University Distinguished Professor of Chemistry David G.I. Kingston has succeeded in enhancing the structure of paclitaxel (Taxol(TM)) to make it more effective in killing cancer cells ...
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Title: Pharmacogenetics of Irinotecan. VOLUME: 3 ISSUE: 3. Author(s):G. Toffoli, E. Cecchin, G. Corona and M. Boiocchi. Affiliation:Experimental and Clinical Pharmacology, Unit CRO-National Cancer Institute, 33081 Aviano-PN,Italy.. Keywords:pharmacogenetics, irinotecan, ugt1a1, cyp3a4, hce, mrp2, mdr1 polymorphisms. Abstract: Pharmacogenetics focuses on intersubjects variation in therapeutic drug effects and toxicity depending on genetic polymorphisms. This is particularly interesting in oncology since anticancer drugs usually have a narrow margin of safety. Irinotecan {7-ethyl-10-[4-(1- piperidino)-1-piperidino]carbonyloxycamptothecin} is used in cancer chemotherapy as a topoisomerase I inhibitor and it is characterised by a sometimes unpredictable severe toxicity. It is mostly intestinal with nausea, vomit and diarrhoea or haematologic with leukothrombocytopenia. Its complex metabolism involves many proteins. Human carboxylesterase isoforms 1 and 2 (hCE1, hCE2) activate irinotecan to its ...
TY - JOUR. T1 - Omacetaxine mepesuccinate in patients with advanced chronic myeloid leukemia with resistance or intolerance to tyrosine kinase inhibitors. AU - Khoury, H. Jean. AU - Cortes, Jorge. AU - Baccarani, Michele. AU - Wetzler, Meir. AU - Masszi, Tamas. AU - Digumarti, Raghunadharao. AU - Craig, Adam. AU - Benichou, Annie Claude. AU - Akard, Luke. PY - 2015/1/1. Y1 - 2015/1/1. N2 - Omacetaxine mepesuccinate promotes apoptosis by inhibiting the production of short-lived oncoproteins. The efficacy and safety of omacetaxine in patients with advanced chronic myeloid leukemia (CML) previously treated with tyrosine kinase inhibitors were assessed in two phase II trials (CML-202 and CML-203). Fifty-one patients in accelerated phase (AP-CML) and 44 in myeloid blast phase (BP-CML) received subcutaneous omacetaxine 1.25 mg/m2 twice daily days 1-14 every 28 days until hematologic response/improvement or any cytogenetic response, then days 1-7 every 28 days until disease progression. The primary ...
Camptothecin analogues showing more potent anti-tumor activity than a naturally occurring alkaloid camptothecin, which also exhibit an immunosuppressive activity, in which the 1-ethyl of camptothecin is replaced by various members of substitutents such as alkyls (except ethyl), alkenyls, alkynyls, aralkyls or aryloylalkyls; being produced from readily accessible starting materials on totally synthetic method newly developed by the present inventor.
TY - JOUR. T1 - Determination of the glucuronide metabolites of the topoisomerase I inhibitors, 7-ethyl-10-hydroxy-camptothecin (SN-38) and NU-ICRF 505 by high performance liquid chromatography. AU - Cummings, J.. AU - Ethell, B T.. AU - Boyd, Gary. AU - Burchell, B.. AU - Smyth, J F.. AU - Jodrell, D I.. PY - 2002. Y1 - 2002. N2 - HPLC methods are presented for the determination of the topoisomerase I inhibitors 7-ethyl 10-hydroxycamptothecin (SN-38) and NU/ICRF 505, their chemical/enzymatic hydrolysis products and glucuronide metabolites in both aqueous media and biological specimens. Chromatographic conditions were optimised for baseline resolution of the water-soluble metabolites from their non-water soluble parent compounds while eetaining compatibility with both atmospheric pressure electrospray ionisation and electron impact ionisation mass spectrometric detection. Solid phase extraction sample preparation utilising a C2-bonded silica sorbent enabled simultaneous recovery of parent ...
Advanced small cell lung cancer (SCLC) has a dismal prognosis. Modulation of the camptothecin topotecan, approved for second-line therapy, may improve response. Our recent finding of synergistic enhancement of the cytotoxic activity of camptothecin (CPT) by cyclin-dependent kinase 4 inhibitors is extended here to a panel of camptothecin analogs comprising 10-hydroxy-CPT (HOCPT), topotecan (TPT; 9-[(dimethylamino)-methyl]-10-hydroxy-CPT), 9-amino-CPT (9AC), 9-nitrocamptothecin (rubitecan), SN38 (7-ethyl-10-hydroxycamptothecin) and 10-hydroxy-9-nitrocamptothecin (CPT109) in combination with PD0332991, CDK4I, roscovitine and olomoucine. SCLC cell lines employed are chemoresistant NCI-H417 and DMS153 and the chemosensitive SCLC26A line established at our institution. The CPT analogs exhibiting highest cytotoxicity towards the three SCLC lines tested were SN38 and 9AC, followed by rubitecan, HOCPT, TPT and CPT109. NCI-H417 and DMS153 revealed an approximately 25-fold and 7-fold higher resistance compared to

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Podofilox, also called podophyllotoxin, is a purer and more stable form of podophyllin in which only the biologically active portion of the compound is present. Podofilox is used to remove certain types of warts on the outside skin of the genital areas ...
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Podofilox, also called podophyllotoxin, is a purer and more stable form of podophyllin in which only the biologically active portion of the compound is present. Podofilox is used to remove certain types of warts on the outside skin of the genital areas ...
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Evaluation of the Safety and Tolerability of TAK-228 With TAK-117 and Paclitaxel in Advanced Solid Tumors - Full Text View -...Evaluation of the Safety and Tolerability of TAK-228 With TAK-117 and Paclitaxel in Advanced Solid Tumors - Full Text View -...

Antineoplastic Agents, Phytogenic. Antineoplastic Agents. Tubulin Modulators. Antimitotic Agents. Mitosis Modulators. Molecular ... Use of anti-hypertensive agents to control hypertension before Cycle1 Day 1 is allowed. ...
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Efficacy of HIPEC in the Treatment of Locally Advanced Gastric Cancer After radIcal Gastrectomy With D2 - Full Text View -...Efficacy of HIPEC in the Treatment of Locally Advanced Gastric Cancer After radIcal Gastrectomy With D2 - Full Text View -...

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RCSB PDB - VLB Ligand Summary PageRCSB PDB - VLB Ligand Summary Page

Antineoplastic Agents. *Antineoplastic Agents, Phytogenic. *Antineoplastic and Immunomodulating Agents. *BSEP/ABCB11 Inhibitors ... Vinblastine is a vinca alkaloid antineoplastic agent. The vinca alkaloids are structurally similar compounds comprised of 2 ...
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Antineoplastic Agents, Phytogenic. *Humans. *Medicine, Ayurvedic. *Neoplasms. *Plants, Medicinal. Notes:. * An integrated ... injectable agents, such as botox, fibrel, autologous fat grafting as also few surgical procedures have been used. Ayurveda, the ... injectable agents, such as botox, fibrel, autologous fat grafting as also few surgical procedures have been used. Ayurveda, the ...
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Characterization of thiol-conjugated metabolites of ginger components shogaols in mouse and human urine and modulation of the...Characterization of thiol-conjugated metabolites of ginger components shogaols in mouse and human urine and modulation of the...

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Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt...Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt...

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Phytogenic; three paclitaxel molecules linked by a cleavable succinyl ester linkage to a brain peptide vector, Angiopep-2, ... Antineoplastic Agents, Phytogenic; three paclitaxel molecules linked by a cleavable succinyl ester linkage to a brain peptide ... Bio-Agent Context: Research Results. *Organic Chemicals: 58*Hydrocarbons: 412*Terpenes: 260*Diterpenes: 237*Taxoids: 1654* ... 09/01/2008 - "ANG1005 has an antineoplastic potency similar to that of paclitaxel against human cancer cell lines. ". ...
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Silymarin; Prostatic Neoplasms; Antioxidants; Apoptosis; Antineoplastic Agents, Phytogenic Department: 336-716-2011 ... Syringes; Virus Diseases; Hospitals, Veterans; Cross Infection; Hypoglycemic Agents Academic: 336-716-0691. Department: 704-638 ...
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3-year results of docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer: a...3-year results of docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer: a...

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Pharmacology of Oleanolic Acid and Ursolic Acid - PubMedPharmacology of Oleanolic Acid and Ursolic Acid - PubMed

Antineoplastic Agents, Phytogenic / pharmacology *. Actions. * Search in PubMed * Search in MeSH * Add to Search ... In this study, we confirmed that oleanolic acid can be an effective agent for the prevention of acute lung injury generated via ...
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Bioflavonoids as Poisons of Human Topoisomerase II Alpha and II Beta - PubMedBioflavonoids as Poisons of Human Topoisomerase II Alpha and II Beta - PubMed

Antineoplastic Agents, Phytogenic / toxicity Actions. * Search in PubMed * Search in MeSH * Add to Search ... Recent Developments of DNA Poisons--Human DNA Topoisomerase IIα Inhibitors--As Anticancer Agents B Pogorelčnik et al. Curr ...
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adenocarcinoma of sigmoid colon disorder 2005:2010[pubdate] *count=100 - BioMedLib™ search engineadenocarcinoma of sigmoid colon disorder 2005:2010[pubdate] *count=100 - BioMedLib™ search engine

Antineoplastic Agents; 0 / Antineoplastic Agents, Phytogenic; 0 / Organoplatinum Compounds; 2S9ZZM9Q9V / Bevacizumab; ... Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / Antineoplastic Agents, Phytogenic; 7673326042 / irinotecan; ... Antimetabolites, Antineoplastic / administration & dosage. Antimetabolites, Antineoplastic / therapeutic use. Chemotherapy, ... Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Lung Neoplasms / drug therapy. Lung Neoplasms / secondary. ...
more infohttp://www.bmlsearch.com/?kwr=adenocarcinoma+of+sigmoid+colon+disorder+2005:2010%5Bpubdate%5D&cxts=100&stmp=b0

tumor of aortic body drug therapy 2000:2010[pubdate] *count=100 - BioMedLib™ search enginetumor of aortic body drug therapy 2000:2010[pubdate] *count=100 - BioMedLib™ search engine

Antineoplastic Agents, Phytogenic / adverse effects. Antineoplastic Agents, Phytogenic / therapeutic use. Carcinoma, ... Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Antineoplastic Agents, Phytogenic; P88XT4IS4D / Paclitaxel; Q20Q21Q62J ... Antimetabolites, Antineoplastic / administration & dosage. Antineoplastic Agents / administration & dosage. Antineoplastic ... Antineoplastic Agents, Phytogenic / pharmacology. Cell Line, Tumor. Cell Movement / drug effects. Cell Proliferation / drug ...
more infohttp://www.bmlsearch.com/?kwr=tumor+of+aortic+body+drug+therapy+2000:2010%5Bpubdate%5D&cxts=100&stmp=b1

Adelaide Research & Scholarship: Irinotecan-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and...Adelaide Research & Scholarship: Irinotecan-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and...

Antineoplastic Agents, Phytogenic; Treatment Outcome; Odds Ratio; Risk Assessment; Risk Factors; Reproducibility of Results; ...
more infohttps://digital.library.adelaide.edu.au/dspace/handle/2440/116335

Translational activation in T-ALLa-c) Diagram of muta | Open-iTranslational activation in T-ALLa-c) Diagram of muta | Open-i

Antineoplastic Agents, Phytogenic/pharmacology/therapeutic use. *Base Sequence. *Cell Line, Tumor. *Epigenesis, Genetic ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC4492470_nihms635519f6&req=4

Analysis of morphological changes in oleanolic acid-tre | Open-iAnalysis of morphological changes in oleanolic acid-tre | Open-i

Antineoplastic Agents, Phytogenic/pharmacology*. *Apoptosis/drug effects*. *Cell Cycle Checkpoints/drug effects* ... Therefore, oleanolic acid may be used as a therapeutic agent in the treatment of human HCC. ... Therefore, oleanolic acid may be used as a therapeutic agent in the treatment of human HCC. ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC4581805_MMR-12-04-5012-g04&req=4
  • This article reviews the literature pertaining to Withania somnifera and its botanical constituents as antitumor agents and in conjunction with radiation and chemotherapy treatment. (nih.gov)