Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.Injections, Intravenous: Injections made into a vein for therapeutic or experimental purposes.United States Food and Drug Administration: An agency of the PUBLIC HEALTH SERVICE concerned with the overall planning, promoting, and administering of programs pertaining to maintaining standards of quality of foods, drugs, therapeutic devices, etc.Drug Administration Routes: The various ways of administering a drug or other chemical to a site in a patient or animal from where the chemical is absorbed into the blood and delivered to the target tissue.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Administration, Intranasal: Delivery of medications through the nasal mucosa.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Injections, Intraperitoneal: Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Injections, Subcutaneous: Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.Administration, Rectal: The insertion of drugs into the rectum, usually for confused or incompetent patients, like children, infants, and the very old or comatose.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Mice, Inbred C57BLBiological Availability: The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.Injections, Intramuscular: Forceful administration into a muscle of liquid medication, nutrient, or other fluid through a hollow needle piercing the muscle and any tissue covering it.Administration, Topical: The application of drug preparations to the surfaces of the body, especially the skin (ADMINISTRATION, CUTANEOUS) or mucous membranes. This method of treatment is used to avoid systemic side effects when high doses are required at a localized area or as an alternative systemic administration route, to avoid hepatic processing for example.Infusions, Intravenous: The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.Administration, Intravenous: Delivery of substances through VENIPUNCTURE into the VEINS.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Area Under Curve: A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)Injections, Intraventricular: Injections into the cerebral ventricles.Mice, Inbred BALB CRats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Administration, Cutaneous: The application of suitable drug dosage forms to the skin for either local or systemic effects.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Double-Blind Method: A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.Cross-Over Studies: Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Administration, Sublingual: Administration of a soluble dosage form by placement under the tongue.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Administration, Inhalation: The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Infusions, Parenteral: The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects.Behavior, Animal: The observable response an animal makes to any situation.Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.Injections: Introduction of substances into the body using a needle and syringe.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Injections, Spinal: Introduction of therapeutic agents into the spinal region using a needle and syringe.Organ Size: The measurement of an organ in volume, mass, or heaviness.Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.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.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Mice, Inbred ICRLung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Rats, Inbred F344Analgesics, Opioid: Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal.Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Estradiol: The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Drug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.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.Injections, Intra-Arterial: Delivery of drugs into an artery.Administration, Buccal: Administration of a soluble dosage form between the cheek and gingiva. It may involve direct application of a drug onto the buccal mucosa, as by painting or spraying.Spleen: An encapsulated lymphatic organ through which venous blood filters.Piperidines: A family of hexahydropyridines.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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Intestinal Absorption: Uptake of substances through the lining of the INTESTINES.Blood Glucose: Glucose in blood.Drug Approval: Process that is gone through in order for a drug to receive approval by a government regulatory agency. This includes any required pre-clinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance of the drug.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.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Eating: The consumption of edible substances.United StatesDopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Genetic Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Hydrocortisone: The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Absorption: The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.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.Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Delayed-Action Preparations: Dosage forms of a drug that act over a period of time by controlled-release processes or technology.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Pain Measurement: Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.Pain: An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.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.Testosterone: A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.Anti-Inflammatory Agents: Substances that reduce or suppress INFLAMMATION.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Progesterone: The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.Genetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.Growth Hormone: A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized.Administration, Intravaginal: The insertion of drugs into the vagina to treat local infections, neoplasms, or to induce labor. The dosage forms may include medicated pessaries, irrigation fluids, and suppositories.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Animals, Newborn: Refers to animals in the period of time just after birth.Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.Body Temperature: The measure of the level of heat of a human or animal.Models, Animal: Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.Drug Delivery Systems: Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Kinetics: The rate dynamics in chemical or physical systems.Bile: An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.United States Department of Veterans Affairs: A cabinet department in the Executive Branch of the United States Government concerned with overall planning, promoting, and administering programs pertaining to VETERANS. It was established March 15, 1989 as a Cabinet-level position.Gonadotropin-Releasing Hormone: A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND.Phytotherapy: Use of plants or herbs to treat diseases or to alleviate pain.Drugs, Chinese Herbal: Chinese herbal or plant extracts which are used as drugs to treat diseases or promote general well-being. The concept does not include synthesized compounds manufactured in China.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Luteinizing Hormone: A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity.Diabetes Mellitus, Experimental: Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.PiperazinesNeoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.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.Device Approval: Process that is gone through in order for a device to receive approval by a government regulatory agency. This includes any required preclinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance. It is not restricted to FDA.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.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.Infusion Pumps: Fluid propulsion systems driven mechanically, electrically, or osmotically that are used to inject (or infuse) over time agents into a patient or experimental animal; used routinely in hospitals to maintain a patent intravenous line, to administer antineoplastic agents and other drugs in thromboembolism, heart disease, diabetes mellitus (INSULIN INFUSION SYSTEMS is also available), and other disorders.Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Glucocorticoids: A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.Regional Blood Flow: The flow of BLOOD through or around an organ or region of the body.Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Adjuvants, Immunologic: Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.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.Diazepam: A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.Corticosterone: An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures.Chemistry, Pharmaceutical: Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use.Adrenocorticotropic Hormone: An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).Drug Carriers: Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.Central Nervous System Stimulants: A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here.Ovariectomy: The surgical removal of one or both ovaries.Hyperalgesia: An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Mice, Inbred C3HLeukocyte Count: The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.Hypnotics and Sedatives: Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Analgesics, Non-Narcotic: A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)Drug-Induced Liver Injury: A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Anti-Anxiety Agents: Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.Brain Chemistry: Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.Placebos: Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol.Suppositories: Medicated dosage forms that are designed to be inserted into the rectal, vaginal, or urethral orifice of the body for absorption. Generally, the active ingredients are packaged in dosage forms containing fatty bases such as cocoa butter, hydrogenated oil, or glycerogelatin that are solid at room temperature but melt or dissolve at body temperature.Hypothalamus: Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Substance Withdrawal Syndrome: Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.Adenoviridae: A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.Edema: Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Infusion Pumps, Implantable: Implanted fluid propulsion systems with self-contained power source for providing long-term controlled-rate delivery of drugs such as chemotherapeutic agents or analgesics. Delivery rate may be externally controlled or osmotically or peristatically controlled with the aid of transcutaneous monitoring.Chorionic Gonadotropin: A gonadotropic glycoprotein hormone produced primarily by the PLACENTA. Similar to the pituitary LUTEINIZING HORMONE in structure and function, chorionic gonadotropin is involved in maintaining the CORPUS LUTEUM during pregnancy. CG consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is virtually identical to the alpha subunits of the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity (CHORIONIC GONADOTROPIN, BETA SUBUNIT, HUMAN).Feces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.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.Narcotics: Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).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.Erythropoietin: Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.Acute Disease: Disease having a short and relatively severe course.Hypoglycemic Agents: Substances which lower blood glucose levels.Rats, Inbred LewEndotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.Sulfonamides: A group of compounds that contain the structure SO2NH2.Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.Injections, Intradermal: The forcing into the skin of liquid medication, nutrient, or other fluid through a hollow needle, piercing the top skin layer.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.

Metronomic oral topotecan with pazopanib is an active antiangiogenic regimen in mouse models of aggressive pediatric solid tumor. (1/24)

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The tumor microenvironment expression of p-STAT3 influences the efficacy of cyclophosphamide with WP1066 in murine melanoma models. (2/24)

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Prognostic and predictive value of clinical and biochemical factors in breast cancer patients with bone metastases receiving "metronomic" zoledronic acid. (3/24)

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Pilot study of a pediatric metronomic 4-drug regimen. (4/24)

BACKGROUND: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. MC is gaining interest as an alternative strategy to fight resistant cancer. OBJECTIVE: to assess the safety of 4 drug MC regimen in paediatric patients with refractory or relapsing various tumour types. SETTING: From November 2008 to December 2010, in three academic paediatric oncology centers, 16 children (median age 12 years old; range 5.5-20) were included in this pilot study. This treatment was proposed to children with refractory disease for whom no further effective treatments were available. Most frequent diagnosis were medulloblastoma/cerebral PNET (5) osteosarcoma (5), and one case each of nephroblastoma, high grade glioma, Hodgkin lymphoma, rhabdomyosarcoma, neuroblastoma and kidney rhabdoid tumour. The MC regimen consisted in cycles of 56 days (8 weeks) with weekly vinblastine 3 mg/m2 (week 1-7), daily cyclophosphamide 30 mg/m2 (days 1-21), and twice weekly methotrexate 10 mg/m(2) (days 21-42), and daily celecoxib 100 mg to 400 mg twice daily (days 1-56) followed by a 2-weeks chemotherapy break. Adverse events were determined through laboratory analysis and investigator observations. RESULTS: One objective response was observed in a patient with Hodgkin lymphoma, and 4 patients experienced disease stabilization and continued their treatment for 3 cycles (24 weeks) or more. At last follow-up, 7 patients (43%) are alive including 1 still undergoing treatment. During the overall 36 cycles of treatments received by patients, 4 grade IV toxicities and 24 grade III toxicities were observed in 11 cycles in only 10 different patients. CONCLUSION: The metronomic regimen we report here was well tolerated and associated with disease stabilization. This regimen is currently being evaluated in a national multicenter phase II study.  (+info)

VEGF receptor inhibitors block the ability of metronomically dosed cyclophosphamide to activate innate immunity-induced tumor regression. (5/24)

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A phase I study of veliparib in combination with metronomic cyclophosphamide in adults with refractory solid tumors and lymphomas. (6/24)

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Efficacy and safety of metronomic chemotherapy for patients with advanced primary hepatocellular carcinoma with major portal vein tumor thrombosis. (7/24)

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Metronomic oral topotecan prolongs survival and reduces liver metastasis in improved preclinical orthotopic and adjuvant therapy colon cancer models. (8/24)

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Metronomic cyclophosphamide given on an intermittent, 6-day repeating schedule, but not on an exposure dose-equivalent daily schedule, activates an anti-tumor innate immune response that leads to major regression of large implanted gliomas, without anti-angiogenesis. Mice bearing implanted 9L gliomas were used to investigate the effects of this 6-day repeating, immunogenic cyclophosphamide schedule on myeloid-derived suppressor cells, which are pro-angiogenic and can inhibit anti-tumor immunity, and to elucidate the mechanism whereby the innate immune cell-dependent tumor regression response to metronomic cyclophosphamide treatment is blocked by several anti-angiogenic receptor tyrosine kinase inhibitors. Intermittent metronomic cyclophosphamide scheduling strongly increased glioma-associated CD11b+ immune cells but not CD11b+Gr1+ myeloid-derived suppressor cells, while bone marrow and spleen reservoirs of the suppressor cells were decreased. The inhibition of immune cell recruitment and tumor
BACKGROUND: Docetaxel (DTX) and zoledronic acid (ZOL) are effective in patients with hormone resistant prostate cancer (HRPC) with bone metastases. A phase I clinical trial of metronomic administration of Zoledronic Acid AN d TaxoterE combination (ZANTE trial) in 2 different sequences was conducted in HRPC. RESULTS: The maximum tolerated dose was not achieved with sequence A. Two patients at third level of sequence B developed dose limiting toxicity. A disease control was obtained in six out of nine patients treated with sequence A, where a decrease of biological markers and PSA were also observed. No evidence of anti-tumor activity was observed in patients treated with sequence B. PATIENTS AND METHODS: Twenty-two patients enrolled into the study (median age: 73 years; range: 43-80) received one of three escalated doses of DTX (30, 40 and 50 mg/m(2)) in combination with a fixed dose of ZOL (2 mg), both administered every 14 days in two different sequences: DTX at the day 1 followed by ZOL at the ...
RATIONALE: Monoclonal antibodies, such as bevacizumab, 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. Drugs used in chemotherapy, such as paclitaxel, cyclophosphamide, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether bevacizumab is more effective when given together with paclitaxel or cyclophosphamide and capecitabine in treating patients with breast cancer.. PURPOSE: This randomized phase III trial is studying the side effects of giving bevacizumab together with paclitaxel and to see how well it works compared with giving bevacizumab together with cyclophosphamide and capecitabine as first-line therapy in treating women with locally advanced, recurrent, or metastatic breast cancer. ...
International Neuroblastoma Research and Collaboration for Effective Delivery (INBRACED) is a new collaboration between charities, researchers and clinicians with the shared aim of accelerating the development of new, more effective therapies for the childhood cancer neuroblastoma.Central to the groups activities is the introduction of standardised, international clinical trials.
The purpose of this research study is to determine the safety and tolerability of the combination of Zactima with metronomic chemotherapy. Zactima is an oral anti-angiogenesis drug, which means it fights cancer by cutting off a tumors blood supply. Thus, the drug starves the tumor by preventing the delivery of nutrients and oxygen. Metronomic chemotherapy is low dose oral chemotherapy pills which are taken daily. Unlike traditional chemotherapy, metronomic chemotherapy is thought to fight cancer like Zactima, by cutting off the blood supply to tumors. Because the dose is very low, the side effects are generally mild and very different from those with higher dose chemotherapy given by vein ...
An increasing knowledge of cancer biology, coupled with the emerging era of targeted drug therapy, has inspired investigation of specific anti-cancer effects inherent in traditional cytotoxic chemotherapy drugs. The prolonged administration of low doses of chemotherapy with a greatly reduced break period between doses has come to be known as metronomic administration. This strategy represents an attempt to capitalise on effects that chemotherapy may have on the tumour microenvironment. The low cost, ease of administration, and generally well-tolerated adverse event profile has made metronomic administration of chemotherapy drugs appealing in veterinary oncology. However, to date formal clinical evaluation of this treatment strategy is in the early stages and a complete understanding of the types of cancers that are sensitive to treatment, as well as the optimal drugs and dosages to utilize requires further study in rigorous clinical trials.. Conventional dose and scheduling of chemotherapy has ...
This phase II trial studies how well pembrolizumab, bevacizumab, and cyclophosphamide work in treating patients with ovarian, fallopian tube, or primary
Between 11/2010 and 12/2011, 16 pts were included. The trial was closed early because we observed only 5 responses after 4 cycles. Median age was 34 years (18-77). The median number of previous lines was 5 (2-6). Ten pts were primary refractory and 11 were refractory at inclusion. Twelve pts were R/R a median of 5 months after ASCT and 4 pts never had achieved a chemosensitive status. Five pts had also received aloSCT. Twelve pts presented with extranodal disease at inclusion. A total of 110 cycles were administered, with serious (grade ≥ 3) toxicity in 43 cycles (39%). The most frequent serious toxicities were neutropenia (14% of cycles) and thrombocytopenia (7% of cycles). A toxic death was observed after a septic shock in a non neutropenic pt. An ORR of 38% (1 CR and 5 PR) was observed and 10 pts (62%) achieved clinical benefit (response or disease stabilization for more than 6 months). Median progression free survival (PFS) and overall survival (OS) were 7 and 19 months. With a median ...
The combination of trastuzumab with chemotherapeutic agents is a well established approach for treatment of HER2 positive metastatic breast cancer. Preclinical models and subsequent clinical data have demonstrated an additive or synergistic effect of the combination with platinum salts, paclitaxel, docetaxel, vinorelbine or more than one drugs [15-18].. Unfortunately, the success of these combinations in responding patients is compromised by the development of acquired resistance [4]. The mechanism of resistance to trastuzumab in animal models is the consequence of heritable genetic alterations and involved different, independent mechanisms [19]. The opportunity, in patients with progressive disease, of continuing trastuzumab combined with a non cross resistant chemotherapeutic regimen is a crucial question regarding trastuzumab strategy. Data on restored efficacy of trastuzumab with further associations after failure are limited, although some activity was recently reported in patients with ...
This trial is entitled "Metronomic chemotherapy with cyclophosphamide and celecoxib in breast cancer patients progressing after standard chemotherapy:
Metronomic chemotherapy entails the chronic administration of low-dosages of chemotherapy, so theoretically the inhibitory impact on the tumor blood vessel growth is maintained, but the dose is insufficient to cause damage to healthy cells. How can this form of therapy be best utilized to treat pets with cancer?
Tumor necrosis element α (TNF-α)is a bunch inflammatory aspect. gene appearance after TNF-α 18-hour treatment in … TNF-α pretreated Salmonella adjustments the web host response We additional hypothesized that TNF-α treatment adjustments Salmonella effector proteins appearance thus changing Veliparib the hosts inflammatory replies. The c-Jun N-terminal kinase (JNK) pathway may be regulated with the Veliparib Salmonella effector AvrA [29 71 Salmonella Veliparib boosts JNK phosphorylation [29]. We examined for the alteration of the two pathways as read-outs of inflammatory Veliparib replies from web host cells. We discovered that TNF-α pretreated Salmonella SL1344 could enhance c-JUN p-c-JUN and p-JNK appearance in HCT116 cells (Fig. ?(Fig.5A).5A). Statistical data additional showed a big change in appearance of p-c-JUN and p-JNK induced by Salmonella with or without TNF-α treatment (Fig. ?(Fig.5B5B and ?and5C).5C). Moreover the function is confirmed by us of JNK pathway using a JNK ...
AbbVie Announces Topline Results from Two Phase 3 Studies Investigating Veliparib in Combination with Chemotherapy for the Treatment of Patients with Advanced or Metastatic Squamous Non-Small Cell Lung Cancer and Early-Stage Triple-Negative Breast Cancer
... from Bill: Many have cancer, but few progress to true disease | HarvardScience NOVA Online | Cancer Warrior | Watch the Program Antiangiogenic Chemotherapy: Low-dose Metronomic Combined with Intermittent Bolus-dose Cyclophosphamide Is Thrombospondin 1, a mediator of the antiangiogenic effects of low-dose metrono The Anti-Angiogenic Basis of Metronomic Chemotherapy http://www.pnas.org/content/100/22/12917.full Cancer…
Prednisone 60 mg/m2 PO day 1  14. The chemotherapy was cycled every 28 days.. Several palliative lymphoma regimens were developed since but few were all-oral. A CCEP regimen (using Procarbazine instead of Prednisone) was used in AIDS-related non-Hodgkins lymphoma at 6 week intervals. (4) The response rate was 61% with a 39% complete response rate. However the treatment related mortality was high at 11% with myelosuppression being the most frequent and severe toxicity. Similarly, a study in Africa utilizing these agents on different schedules revealed an overall response rate of 78% with an overall survival time of 12.3 months. 33% of these patients with AIDS-related non-Hodgkins lymphoma survived 5 years.(5) Another protocol, PEPC, used Procarbazine in place of CCNU and was administered as metronomic therapy.(6,7) The overall response rate was 69% with a 36% complete response rate and a 33% partial response rate. No treatment related deaths were reported though myelosuppression was still ...
Cyclophosphamide treatment on a six-day repeating metronomic schedule induces a dramatic, innate immune cell-dependent regression of implanted gliomas. However, little is known about the underlying mechanisms whereby metronomic cyclophosphamide induces innate immune cell mobilization and recruitment, or about the role of DNA damage and cell stress response pathways in eliciting the immune responses linked to tumor regression. Untreated and metronomic cyclophosphamide-treated human U251 glioblastoma xenografts were analyzed on human microarrays at two treatment time points to identify responsive tumor cell-specific factors and their upstream regulators. Mouse microarray analysis across two glioma models (human U251, rat 9L) was used to identify host factors and gene networks that contribute to the observed immune and tumor regression responses. Metronomic cyclophosphamide increased expression of tumor cell-derived DNA damage, cell stress, and cell death genes, which may facilitate innate immune
This phase II clinical trial is studying the how well veliparib, topotecan hydrochloride, and filgrastim or pegfilgrastim work in treating patients with
For breast cancers not responsive to Herceptin, or HER2 negative, Kadcyla isnt much use. AbbVie has a Phase 2 candidate that looks like it can fill the gap. During the San Antonio Breast Cancer Symposium last December, AbbVie presented some encouraging data from a Phase 2 study including veliparib, or ABT-888. The I-SPY 2 trial employed an adaptive design to screen for compounds that will be superior to chemotherapy alone, for specific cancer signatures.. Based on the responses seen in 115 patients, AbbVies veliparib combined with carboplatin and chemotherapy showed a 90% probability of being superior to chemotherapy alone in triple-negative patients. It is possible that carboplatin alone, and not veliparib, was responsible, but I doubt it. Carboplatin has been available for over 20 years. It is very likely that Veliparib will enter Phase 3 trials.. Final thoughts ...
Veliparib, also known as ABT-888, is a poly(ADP-ribose) polymerase (PARP) -1 and -2 inhibitor with chemosensitizing and antitumor activities. With no antiproliferative effects as a single agent at therapeutic concentrations, ABT-888 inhibits PARPs, thereby inhibiting DNA repair and potentiating the cytotoxicity of DNA-damaging agents.
This randomized phase II trial studies how well cisplatin works with or without veliparib in treating patients with triple-negative breast cancer and/or B
The IUPHAR/BPS Guide to Pharmacology. veliparib ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs.
In order for tumor cells to multiple and spread, they must develop their own blood supply through a process called angiogenesis. Angiogenesis inhibitor chemotherapy drugs work to stop or slow down this process, thereby controlling tumor growth. Metronomic chemotherapy is one example of angiogenesis inhibition treatment, which is becoming a popular treatment option for pets…
Do pets experience side effects from chemo? Animals can experience vomiting and diarrhea, but they dont lose their hair like people do. There are also several medications that can help reduce these symptoms. I like to start the dosage off very low and build up from there. I do my best to tailor the treatment to the individual pet and what he or she can safely handle. Metronomic chemotherapy is a low-dose oral treatment that can help slow down the growth of blood vessels in tumors and prevent spreading. It is typically a more affordable option and has minimal to no side effects.. What is palliative radiation? There are two types of radiation, definitive and palliative. Palliative is mainly used for pain management, especially in cases of osteocarcinoma, or bone cancer. It can also be used in soft tissue to help slow down growth. The costs are high for a full course of definitive radiation - usually between $5,000 and $7,000. Palliative treatment runs $1,500 to $2,000. How can we tell if our ...
Authors: Brian G Czito, Dustin A Deming, Gayle S Jameson, Mary F Mulcahy, Houman Vaghefi, Matthew W Dudley, Kyle D Holen, Angela DeLuca, Rajendar K Mittapalli, Wijith Munasinghe, Lei He, John R Zalcberg, Samuel Y Ngan, Philip Komarnitsky, Michael Michael
Show all volumes and issues. Tables of content are generated automatically and are based on records of articles contained that are available in the TIB-Portal index. Due to missing records of articles, the volume display may be incomplete, even though the whole journal is available at TIB.. ...
Previs, Rebecca A. et al "Dual Metronomic Chemotherapy with Nab-Paclitaxel and Topotecan Has Potent Antiangiogenic Activity in Ovarian Cancer." Molecular Cancer Therapeutics 14.12 (2015): 2677-2686. Web. 09 Aug. 2020. ...
Clinical trial focusing on veliparib and topotecan. Veliparib and Topotecan for Relapsed Ovarian Cancer With Negative or Unknown BRCA Status
Purpose: Low-dose metronomic chemotherapy treatments, especially when combined with dedicated antiangiogenic agents, can induce significant antitumor activity without serious toxicity in various preclinical models. It remains unclear, however, whether some cytotoxic drugs are better suited for metronomic regimens than others. Paclitaxel appears to be a strong candidate for metronomic chemotherapy given its ability to inhibit endothelial cell functions relevant to angiogenesis in vitro at extraordinarily low concentrations and broad-spectrum antitumor activity. Clinically relevant concentrations of the formulation vehicle cremophor EL in Taxol, however, were previously reported to nullify the antiangiogenic effect of paclitaxel, the result of which would hamper its usefulness in metronomic regimens. We hypothesized that ABI-007, a cremophor EL-free, albumin-bound, 130-nm form of paclitaxel, could potentially alleviate this problem.. Experimental Design: The antiangiogenic activity of ABI-007 ...
Background: Poly (ADP-ribose) polymerase (PARP) is essential for recognition and repair of DNA damage. In preclinical models, PARP inhibitors modulate topoisomerase I inhibitormediated DNA damage. This Phase I study determined the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics (PK) and pharmacodynamics (PD) of veliparib, an orally-bioavailable PARP 1/2 inhibitor, in combination with irinotecan. Methods: Patients with advanced solid tumors were treated with 100 mg/m2 irinotecan on days 1 and 8 of a 21-day cycle. Twice-daily (BID) oral dosing of veliparib (10-50 mg) occurred days 3- 14 (Cycle 1) and days -1-14 (subsequent cycles) followed by a 6-day rest. PK studies were conducted with both agents alone and in combination. Paired tumor biopsies were obtained after irinotecan alone and veliparib/irinotecan to evaluate PARP1/2 inhibition and explore DNA damage signals (nuclear gamma-H2AX and pNBS1). Results: Thirty-five patients were treated. DLTs included fatigue, ...
The study was a collaborative effort between Dr Pasquier and Shripad D. Banavali, MD, professor and head of the Department of Medical and Pediatric Oncology at Tata Memorial Hospital in Mumbai, India. It followed on the heels of their earlier case report of a 69-year-old woman with metastatic angiosarcoma who was treated with a combination of metronomic chemotherapy and propranolol ...
Measurement of huntingtin chromatin recruitment dynamics by fluorescence recovery after photobleaching (FRAP) of the YFP-tagged huntingtin-specific intrabody, nucHCB2, under conditions of oxidative stress and PARP inhibition
In addition to its potential in hepatitis C, the company thinks it has multiple billion-dollar blockbuster opportunities in its pipeline, including therapies for the treatment of cancer.. One of those promising pipeline drugs is ABT-199, which is being studied as a treatment for blood cancers. ABT-199 is currently being evaluated in phase 3 trials in chronic lymphocytic leukemia, or CLL, and the company thinks that ABT-199 could transform CLL treatment by offering the potential for complete responses in some patients. Earlier this year, AbbVie reported that 23% of CLL patients treated with ABT-199 saw complete remission as part of a small, early-stage trial. If all goes as planned, AbbVie could be on track to submit an FDA application for the approval of ABT-199 later this year.. Another of AbbVies late-stage drugs that was highlighted at the conference is Veliparib, a drug that has the potential to enhance the effectiveness of existing chemotherapy. The company has a range of ongoing ...
Immunovaccine Inc., a clinical stage vaccine company, presented positive data from clinical and preclinical vaccine studies, including DPX-Survivac, the companys lead therapeutic cancer vaccine, this weekend at the American Association for Cancer Research (AACR) 2014 Annual Meeting. In a poster presentation, Immunovaccine highlighted results demonstrating that metronomic cyclophosphamide (mCPA), an immune modulating agent, enhanced the immunogenicity of DepoVax™-based vaccines in preclinical cancer models consistent with previously reported Phase I data showing a similar enhancement of DPX-Survivac in patients. Importantly, the animal studies demonstrated the combination therapys ability to eliminate advanced tumors that could not be treated with vaccine or mCPA alone. Tumors exposed to the combination therapy specifically exhibited an increase in T cell activation markers, suggesting increased immune-mediated anti-tumor activity at the tumor site with the vaccine/mCPA therapy and further ...
Veliparib combined with carboplatin (VC) was an experimental regimen evaluated in the biomarker-rich neoadjuvant I-SPY 2 trial for breast cancer. VC showed improved efficacy in the triple negative signature. However, not all triple negative patients achieved pathologic complete response and some HR+HER2- patients responded. Pre-specified analysis of five DNA repair deficiency biomarkers (BRCA1/2 germline mutation; PARPi-7, BRCA1ness, and CIN70 expression signatures; and PARP1 protein) was performed on 116 HER2- patients (VC: 72 and concurrent controls: 44). We also evaluated the 70-gene ultra-high risk signature (MP1/2), one of the biomarkers used to define subtype in the trial. We used logistic modeling to assess biomarker performance. Successful biomarkers were combined using a simple voting scheme to refine the predicted sensitive group and Bayesian modeling used to estimate the pathologic complete response rates. BRCA1/2 germline mutation status associated with VC response, but its low ...
Additional file 1: of PARP inhibitor veliparib and HDAC inhibitor SAHA synergistically co-target the UHRF1/BRCA1 DNA damage repair complex in prostate cancer cells
Learn about the potential side effects of pazopanib. Includes common and rare side effects information for consumers and healthcare professionals.
Background: Metronomic chemotherapy is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. Objective: To assess the anti-tumour activity and toxicity of a 4-drug metronomic regimen in relapsing/refractory pediatric brain tumours (BT) with progression-free survival (PFS) after 2 cycles as primary endpoint. Methods: Patients ≥4 to 25 years of age were included with progressing BT. Treatment consisted of an 8-week cycle of celecoxib, vinblastine, and cyclophosphamide alternating with methotrexate. Kepner and Chang two-steps model was used with 10 patients in the first stage. If stabilization was observed in ≥2 patients, 8 additional patients were recruited. Assessment was according WHO criteria with central radiology review. Results: Twenty-nine patients (27 evaluable) were included in 2 groups: ependymoma (group 1, N=8), and miscellaneous BT (group 2): 3 medulloblastoma (MB), 5 high grade glioma (HGG), 11 low ...
The IUPHAR/BPS Guide to Pharmacology. pazopanib ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs.
I need some help with a humidity situation. I live in Colorado, where it is normally very dry and have no issues keeping my Dragons humidity down. The house is cooled with a evaporative cooler(swamp cooler) and its jacked up the humidity substantially. I live in a mother-in-law in the bottom of a house, so Im as far away from it as I can get ...
As reported by Hope S. Rugo, MD, and John W. Park, MD, both of the University of California, San Francisco, and colleagues in The New England Journal of Medicine, the multiarm adaptive randomization phase II I-SPY 2 trial has shown that the addition of veliparib/carboplatin and the addition of neratinib to standard neoadjuvant therapy have met criteria predictive of success in a phase III trial of the same comparators in early breast cancer patients with specific biomarker signatures.1,2. I-SPY 2 Details. In the I-SPY 2 trial, multi-arm adaptive randomization is being used to evaluate the effectiveness of multiple new agents added to standard neoadjuvant chemotherapy in producing pathologic complete response in high-risk stage II to III breast cancer based on biomarker subtypes. The aim of the multi-arm adaptive randomization scheme is to more rapidly and accurately identify experimental regimens with a higher likelihood of success in phase II trials that can include smaller numbers of ...
A Phase II/III Randomized Trial of Veliparib or Placebo in Combination with Adjuvant Temozolomide in Newly Diagnosed Glioblastoma with Mgmt Promoter Hypermethylation. ...
03); **represents significant difference between. group 1%FBS + 10 ng/ml TGF-β1′ and group 1%FBS (P = 0.044). Figure 6 The effects of TGF-β1 on expression levels of PKCα and p38 MAPK. BxPC3 cells were treated with 0.1, 1 and 10 ng/ml TGF-β1 for 10 min, 30 min and 24 h. Total cellular protein was extracted and subjected to western blotting analysis to detect expression of PKCα, phosphorylated-p38/total p38 MAPK and phosphorylated-ERK1/2/total ERK1/2. Bx represents BxPC3 cells and Bx/T represents the stably transfected BxPC3 cells with TGF-β1 plasmid. To determine whether the induced PKCα activity is Veliparib in vivo responsible for the TGF-β1-induced decrease in the sensitivity of BxPC3 cells to cisplatin, we treated the cells with a selective PKCα inhibitor, Gö6976, and assessed TGF-β1-induced drug resistance. We found that inhibition of PKCα. activity could partially reverse TGF-β1-induced drug resistance of BxPC3 cells to cisplatin RGFP966 solubility dmso (Figure 7). Figure ...
Pazopanib is intended for Pharmaceuticals applications. Pazopanib is an oral angiogenesis inhibitor targeting VEGFR and PDGFR. All information about Pazopanib hydrochloride salt is provided in the MSDS. We deliver compounds with high purity levels and a comprehensive Certificate of Analysis. Connect to your member account to consult the documents ...
Pulmonary emphysema, a significant global health problem, is characterized by a loss of alveolar structures. Because VEGF is a trophic factor required for the survival of endothelial cells and is abundantly expressed in the lung, we hypothesized that chronic blockade of VEGF receptors could induce alveolar cell apoptosis and emphysema. Chronic treatment of rats with the VEGF receptor blocker SU5416 led to enlargement of the air spaces, indicative of emphysema. The VEGF receptor inhibitor SU5416 induced alveolar septal cell apoptosis but did not inhibit lung cell proliferation. Viewed by angiography, SU5416-treated rat lungs showed a pruning of the pulmonary arterial tree, although we observed no lung infiltration by inflammatory cells or fibrosis. SU5416 treatment led to a decrease in lung expression of VEGF receptor 2 (VEGFR-2), phosphorylated VEGFR-2, and Akt-1 in the complex with VEGFR-2. Treatment with the caspase inhibitor Z-Asp-CH2-DCB prevented SU5416-induced septal cell apoptosis and ...
The Kantar Health blog is full of insights and perspectives on important healthcare and pharmaceutical topics from world experts in varied disciplines.
Ueda H, Tanaka H, Kida Y, Fukuchi H, Ichinose M (May 2008). "Adjuvant chemotherapy with tegafur/uracil administration after ... "Biweekly oxaliplatin plus 1-day infusional fluorouracil/leucovorin followed by metronomic chemotherapy with tegafur/uracil in ... December 2008). "[Regression of metastatic hepatic cancer from gastric cancer by polysaccharide K and UFT administration-a case ... September 2003). "[Complete disappearance with oral UFT administration of recurrent hepatocellular carcinoma of the remnant ...
Although the administration of the state was rapidly Islamicized and subsumed under the Umayyad Caliphate, in the beginning " ... governed by regular metronomic events such as sunrise and sunset. All physical creation (geti) was thus determined to run ... the Zoroastrians were left with no choice but to either conform or migrate to regions that had a more amicable administration. ...
Vomiting or other condition that interfere with oral administration of TMZ. *Previous or concurrent malignancy, excluding basal ... Metronomic Temozolamide in Patients With Recurrent Glioblastoma. Official Title ICMJE PHASE I-II TRIAL OF METRONOMIC ... Metronomic Temozolamide in Patients With Recurrent Glioblastoma. The recruitment status of this study is unknown. The ... Neurological impairment that precludes comprehension or treatment administration. * ...
Metronomic administration of zoledronic acid and taxotere combination in castration resistant prostate cancer patients: phase I ... Metronomic administration of zoledronic acid and taxotere combination in castration resistant prostate cancer patients: phase I ... A phase I clinical trial of metronomic administration of Zoledronic Acid AN d TaxoterE combination (ZANTE trial) in 2 different ... A phase I clinical trial of metronomic administration of Zoledronic Acid AN d TaxoterE combination (ZANTE trial) in 2 different ...
greater than or equal to 3 weeks (21 days) from procarbazine administration, ... metronomic TMZ 50 mg/ m2 daily plus TG02 doseescalation. Drug: TG02 Phase I: Two treatment arms and several dose levels are ... winner of dd vs metronomic TMZ from phase I alone. Drug: TMZ Phase I: In the MTD finding part, TMZ with two alternate ... Phase I Trial of TG02 Plus Dose-Dense or Metronomic Temozolomide Followed by Randomized Phase II Trial of TG02 Plus ...
Administration, Metronomic. Administration of low doses of a drug or a drug combination over prolonged periods of time usually ... Self Administration. Administration of a drug or chemical by the individual under the direction of a physician. It includes ... Drug Administration Schedule. Time schedule for administration of a drug in order to achieve optimum effectiveness and ... Administration, Topical. The application of drug preparations to the surfaces of the body, especially the skin (ADMINISTRATION ...
Administration of temozolomide: Comparison of conventional and metronomic chemotherapy regimens.. Houy N, Le Grand F. ... Interval of gonadotropin administration for in vitro embryo production from oocytes collected from Holstein calves between 2 ...
Preclinical study continues with both dose density and metronomic administration. Darinaparsin (ZinaparTM or ZIO-101) is a ... Phase II hematology trial with favorable treatment activity in certain lymphomas and in Phase I study with oral administration ...
Due to poor tolerance, a subsequent treatment regimen consisted of metronomic chemotherapy with chlorambucil combined with an ... 2Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, New Brunswick, NJ, ... Unusual Presentation and Increased Survival Using a Complementary/Holistic Approach Combined with Metronomic Chemotherapy. ... clinical trial data are needed to further support the use of a complementary/holistic approach in combination with metronomic ...
... administered in combination with oral metronomic cyclophosphamide (OMC). Patients ≥ 18 years of age with refractory metastatic ... Metronomic chemotherapy refers to the frequent, typically daily, administration of cytotoxic drugs at doses that are ... Oral cyclophosphamide-based metronomic chemotherapy (OMC) is the most largely studied metronomic regimen, with greater than 30 ... The dose of metronomic cyclophosphamide (50 mg twice a day) could be discussed since some prior trials are based on 50-100 mg ...
... administration. Ghiringhelli and colleagues first evaluated the effects of metronomic cyclophosphamide in patients with ... Metronomic Oral Cyclophosphamide. Metronomic oral cyclophosphamide is administered in an iterative low-dose fashion. ... Cyclophosphamide was given either as oral metronomic (50 mg/day), a single i.v. injection (1,000 mg), or both. Metronomic ... metronomic cyclophosphamide results in prolonged Treg suppression, which returns to baseline with continued administration ...
β-hCG Monitoring of B16 Melanoma Experimental Metastases in Mice Undergoing Metronomic Administration of Cyclophosphamide and ... Metronomic administration (20 mg/kg/d) of cyclophosphamide was carried out by addition of the drug to the drinking water as ... The fourth group received the combination of bolus dose plus metronomic cyclophosphamide together with DC101 administration. As ... Treatments involved bolus plus low-dose metronomic cyclophosphamide (BD+LDM CTX; bolus was 150 mg/kg on days 9 and 30; low-dose ...
Imatinib Mesylate And Cyclophosphamide In Metronomic Administration: Dose Escalation Study Of Imatinib Mesylate. *Cancer ... Safety and Efficacy Study Using 5-ALA Oral Administration as an Adjuvant Therapy on the Rate of Local Tumor Recurrence in ... To assess the safety of study drug administration in the study population. To assess the 5 years local recurrence rate. ...
Imatinib Mesylate And Cyclophosphamide In Metronomic Administration: Dose Escalation Study Of Imatinib Mesylate. *Cancer ... Safety and tolerability of C. novyi-NT spore administration in patients with advanced solid tumor malignancies will be measured ...
Imatinib Mesylate And Cyclophosphamide In Metronomic Administration: Dose Escalation Study Of Imatinib Mesylate. *Cancer ...
Imatinib Mesylate And Cyclophosphamide In Metronomic Administration: Dose Escalation Study Of Imatinib Mesylate. *Cancer ...
... we developed a pharmacokinetic/pharmacodynamic mathematical model that identifies in silico the most effective administration ... Both metronomic protocols (0.5 and 1 mg/kg/day for 28 days) were evaluated in chemoresistant neuroblastoma-bearing mice and ... Furthermore, metronomic gemcitabine yielded a 40%-50% decrease in tumor mass at the end of treatment as compared with control ... Despite this, metronomic gemcitabine significantly inhibited tumor angiogenesis and reduced tumor perfusion and inflammation in ...
Metronomic Temozolomide (low-dose, continuous administration) within the past 7 days prior to planned infusion ... Subjects that meet the study eligibility criteria will undergo surgery associated with study drug administration. MDNA55 will ... be performed monthly for the first 6 months and bimonthly thereafter for approximately 1 year after study drug administrations ...
The continuous or "metronomic" schedule required administration of granulocyte colony-stimulating factor (GCSF) as growth ... In July 2010, the US Food and Drug Administration approved everolimus (Afinitor) in combination with exemestane to treat ... Although the precise role of adjuvant taxane therapy remains controversial, the optimal scheduling of taxane administration has ... Preclinical data suggest that metronomic chemotherapy works through an antiangiogenic mechanism, which may explain the apparent ...
Metronomic chemotherapy consists in administration of low doses of chemotherapeuticals with the aim of reducing tumor ... F. Ghiringhelli, C. Menard, P. E. Puig et al., "Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T ... Recently, it has been elucidated that low doses of oral metronomic cyclophosphamide in advanced cancer patients induce a ...
The low cost, ease of administration, and generally well-tolerated adverse event profile has made metronomic administration of ... Tolerability of metronomic administration of lomustine in dogs with cancer. J Vet Intern Med. 2011;25:278-284. ... Metronomic chemotherapy administration may also be a promising approach to combination therapy with emerging targeted agents, ... The principal goal of metronomic administration of chemotherapy is reduction or elimination of the break period between doses. ...
Metronomic Chemotherapy for Canine Osteosarcoma and Other Limb Cancers ... "New Drug Administration Option Improves Treatment Success and Decreases Side Effects.". Its better to hop on three legs than ... A great article about metronomic chemotherapy by oncologist Dr. Joanne Intile:. Understanding Metronomic Chemotherapy for Pets ... Add Reply: Metronomic Chemotherapy for Canine Osteosarcoma and Other Limb Cancers. Please add brief descriptive title for new ...
Metronomic chemotherapy involves the administration of a chemotherapeutic drug at a reduced dose compared with traditional ... Metronomic Cyclophosphamide-Induced Mouse TSP-1 Expression Is Blocked in the Combination Therapy. Metronomic cyclophosphamide ... However, whereas metronomic cyclophosphamide regressed 9L tumors, the combination of axitinib with metronomic cyclophosphamide ... to study the combination of daily axitinib administration with cyclophosphamide given on an every 6-day repeating, metronomic ...
Metronomic administration of zoledronic acid and taxotere combination in castration resistant prostate cancer patients: phase I ...
Purpose Metronomic chemotherapy, at a minimally toxic dose and with a frequent schedule, is a potentially novel approach to the ... Tanaka F, Yanagihara K, Otake Y et al (2004) Angiogenesis and the efficacy of postoperative administration of UFT in pathologic ... Kerbel RS, Kamen BA (2004) The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer 4:423-436PubMedCrossRefGoogle ... Colorectal cancer Tegafur UFT Oxaliplatin Metronomic chemotherapy This is a preview of subscription content, log in to check ...
Combining immune checkpoint inhibition with metronomic administration of chemotherapeutic drugs may create a synergistic effect ... Metronomic chemotherapy can also decrease the number of immunosuppressive cells in the tumor microenvironment, including ... High-frequency low-dose (also known as metronomic) chemotherapy can help improve the activity of CTLs by providing sufficient ... Combining immune checkpoint inhibition with metronomic administration of chemotherapeutic drugs may create a synergistic effect ...
Metronomic administration involves giving low doses of the drug at a higher frequency and is known to have an immunomodulating ... and efficacy of the co-administration of Pexa-Vec with metronomic cyclophosphamide (low doses given with high frequency) in ... Transgene and Institut Bergonié Present a Poster on the METROmaJX Trial (Oncolytic Virus Pexa-Vec + Metronomic Cyclophosphamide ...
  • Large numbers of responsive cytokines, chemokines and immune regulatory genes linked to innate immune cell recruitment and tumor regression were identified, as were several immunosuppressive factors that may contribute to the observed escape of some tumors from metronomic CPA-induced, immune-based regression. (biomedcentral.com)
  • Antiangiogenic therapy of the chimeras bearing established MCF-7 tumors was carried out by i.v. administration of a mAb(s) via the tail vein of mice. (aacrjournals.org)
  • Two similar, large-scale, prospective randomized independent trials designed by the European Organization for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG) were conducted to evaluate the role of concurrent administration of cisplatin with radiation in the postoperative treatment of high-risk head and neck tumors. (careacross.com)
  • Several cytokines and chemokines associated with mobilizing innate immune response cells [ 17 , 18 ] were also identified in these models of metronomic CPA-induced regression, including CXCL14, IL-12β, and CXCL12/SDF1α. (biomedcentral.com)
  • These factors may include useful biomarkers that facilitate discovery of clinically effective immunogenic metronomic drugs and treatment schedules, and the selection of patients most likely to be responsive to immunogenic drug scheduling. (biomedcentral.com)
  • Due to the morbidity observed with DTX1 treatment, it is difficult to clearly ascertain if metronomic schedules will be effective for treatment. (aacrjournals.org)
  • Instead of using short bursts of toxic MTD chemotherapy interspersed with long breaks to allow recovery from the harmful side effects, there is now a shift in thinking towards the view that more compressed or accelerated schedules of drug administration using much smaller dosages than MTD might be more effective-not only in terms of reducing certain toxicities but perhaps even improving antitumor effects as well. (veterinarycancer.com)
  • Often elderly patients with advanced NSCLC have comorbidities, which prevent the administration of standard schedules of chemotherapy. (clinmedjournals.org)
  • Carboplatin, paclitaxel and vinorelbine are the most utilized agents for lung cancer treatment, and the same agents are used also in metronomic schedules [ 4 ]. (clinmedjournals.org)
  • In addition to a direct tumour cell cytotoxic effect, which may still represent a significant mechanism of action, metronomic administration of certain chemotherapy drugs has been shown to modulate specific aspects of the tumour microenvironment. (vin.com)
  • Immunotherapeutic mechanisms for metronomic cyclophosphamide are based on reduction in circulating T regulatory cells that suppress the immune response, and possible concomitant increases in T helper subset 17 (Th17) cells, which translates to a boost in anti-tumour immunity. (vin.com)
  • The agent's oral bioavailability allows for metronomic administration, which could result in sustained insult to tumour vasculature, potentially leading to improved anticancer activity in addition to greater patient convenience. (pressebox.com)
  • Optimal duration of adjuvant Herceptin is still unknown, but we know from a pilot study ( Abstract 2075 ) that prolonged administration (52 weeks in this trial) does not confer a significant advantage. (bcaction.org)
  • The ability to provide frequent administration, most often necessitating oral dosing, is a key component to drug suitability. (vin.com)
  • The invention provides an encapsulated unit dosage form for picoplatin that is adapted for oral administration of the picoplatin containing a substantially dry powder with about 20 to 55 wt % picoplatin in the physical form of a picoplatin particulate wherein an average picoplatin particle diameter is less than about 10 microns. (freepatentsonline.com)
  • 1. A unit dosage form for picoplatin, adapted for oral administration of the picoplatin, comprising a substantially water-soluble capsule shell, the capsule shell enclosing a formulation comprising a substantially dry powder comprising about 10 to 60 wt % particulate picoplatin, a substantially water-soluble, water-dispersible, or water-absorbing carbohydrate, and an effective amount of up to about 5 wt % of a lubricant. (freepatentsonline.com)