The giving of drugs, chemicals, or other substances by mouth.
Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.
Injections made into a vein for therapeutic or experimental purposes.
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.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
Elements of limited time intervals, contributing to particular results or situations.
Delivery of medications through the nasal mucosa.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.
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.
Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.
The insertion of drugs into the rectum, usually for confused or incompetent patients, like children, infants, and the very old or comatose.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
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.
Forceful administration into a muscle of liquid medication, nutrient, or other fluid through a hollow needle piercing the muscle and any tissue covering it.
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.
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.
The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.
Delivery of substances through VENIPUNCTURE into the VEINS.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
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 into the cerebral ventricles.
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.
The application of suitable drug dosage forms to the skin for either local or systemic effects.
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.
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)
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.
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)
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.
PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.
Administration of a soluble dosage form by placement under the tongue.
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.
The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
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.
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.
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.
The observable response an animal makes to any situation.
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.
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.
Proteins prepared by recombinant DNA technology.
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.
Introduction of substances into the body using a needle and syringe.
A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.
Introduction of therapeutic agents into the spinal region using a needle and syringe.
The measurement of an organ in volume, mass, or heaviness.
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.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
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.
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.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.
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.
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.
The number of times the HEART VENTRICLES contract per unit of time, usually per minute.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
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.
The physical activity of a human or an animal as a behavioral phenomenon.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.
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.
The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.
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.
Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.
Compounds capable of relieving pain without the loss of CONSCIOUSNESS.
Therapy with two or more separate preparations given for a combined effect.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Delivery of drugs into an artery.
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.
An encapsulated lymphatic organ through which venous blood filters.
A family of hexahydropyridines.
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 produced by a single clone of cells.
Uptake of substances through the lining of the INTESTINES.
Glucose in blood.
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 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.
The action of a drug in promoting or enhancing the effectiveness of another drug.
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.
A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.
The consumption of edible substances.
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.
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.
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.
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.
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.
The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.
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.
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)
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Dosage forms of a drug that act over a period of time by controlled-release processes or technology.
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).
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.
An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.
The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
A systemic inflammatory response to a variety of clinical insults, characterized by two or more of the following conditions: (1) fever >38 degrees C or HYPOTHERMIA 90 beat/minute; (3) tachypnea >24 breaths/minute; (4) LEUKOCYTOSIS >12,000 cells/cubic mm or 10% immature forms. While usually related to infection, SIRS can also be associated with noninfectious insults such as TRAUMA; BURNS; or PANCREATITIS. If infection is involved, a patient with SIRS is said to have SEPSIS.
Substances that reduce or suppress INFLAMMATION.
Substances that reduce the growth or reproduction of BACTERIA.
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.
An anti-inflammatory 9-fluoro-glucocorticoid.
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.
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.
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.
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.
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.
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.
Refers to animals in the period of time just after birth.
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.
The measure of the level of heat of a human or animal.
Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.
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.
Agents inhibiting the effect of narcotics on the central nervous system.
The rate dynamics in chemical or physical systems.
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.
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.
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.
Use of plants or herbs to treat diseases or to alleviate pain.
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.
Drugs used to cause dilation of the blood vessels.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
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 induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.
Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.
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.
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.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
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.
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.
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.
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.
The flow of BLOOD through or around an organ or region of the body.
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.
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.
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.
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.
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.
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.
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)
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).
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 dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use.
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).
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.
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.
The surgical removal of one or both ovaries.
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.
A synthetic steroid with progestational activity.
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.
Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.
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)
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.
Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.
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.
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.
An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.
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.
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).
Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
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.
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.
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).
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.
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.
Disease having a short and relatively severe course.
Substances which lower blood glucose levels.
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.
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.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
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 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.
A state in south central Australia. Its capital is Adelaide. It was probably first visited by F. Thyssen in 1627. Later discoveries in 1802 and 1830 opened up the southern part. It became a British province in 1836 with this self-descriptive name and became a state in 1901. (From Webster's New Geographical Dictionary, 1988, p1135)
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.
The forcing into the skin of liquid medication, nutrient, or other fluid through a hollow needle, piercing the top skin layer.
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.
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.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.

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
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 ...
Cancers are highly dynamic and adaptive systems that can evolve phenotypic strategies to overcome proliferation barriers in their environment. Application of therapy to the tumor adds an iatrogenic selection force to the adaptive landscape that will inevitably promote evolution of therapy-resistant phenotypic strategies. This evolutionary capacity to develop resistance results in treatment failure and tumor regrowth in the vast majority of cancer patients. Interestingly, despite this well-recognized dynamic and evolutionary nature of tumors, cancer chemotherapy is typically applied through protocols that a priori fix the drug(s), dose, and timing.. Virtually all current chemotherapy regimens have, as a fundamental strategy, the goal of killing maximal numbers of tumor cells. Usually, this is achieved through application of the highest drug dose that results in acceptable patient toxicity. More recently, metronomic therapy has been proposed as an alternative strategy. This approach uses smaller ...
Antiangiogenic therapies can now be regarded as an established antitumor strategy and LDM represents a promising approach in this respect (1), especially when it is combined with targeted antiangiogenic drugs for long-term maintenance-type regimens (9, 10, 15). LDM frequently involves daily oral cytotoxic drug administration, as it is the case with CPA, the clinically most commonly used drug in this treatment setting (1, 3, 8-14). Although the oral route is very practical and appealing, it also raises new challenges, such as treatment compliance by patients and pharmacokinetic issues that potentially differ from conventional, cyclic MTD chemotherapy administration. The findings of our study shed light on several important issues about the clinical translation of the LDM concept.. Previous studies with the PC-3 model suggested that host-mediated mechanisms, such as altered CPA biotransformation, might contribute to acquired resistance to LDM CPA (17). We now show that neither tumor growth ...
This phase II trial studies how well pembrolizumab, bevacizumab, and cyclophosphamide work in treating patients with ovarian, fallopian tube, or primary
Severe immune suppression is frequent in late-stage tumor patients and promotes tumor immune evasion and subsequent tumor progression. Regulatory T cells (Treg) are major suppressors of anti-tumor immune responses. Therefore, targeting of Treg has become a key goal of anti-tumor therapy. Several pre …
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?
Metronomic chemotherapy is an alternative form of chemotherapy in which the patient receives low doses of cytostatics, but for a long time and without interruption.
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 ...
treated by metronomic cyclophosphamide, piroxicam and thalidomide Unresectable or metastatic (advanced) primary pulmonary carcinoma (PPC) represents a...
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
Suggested Readings 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 ...
This randomized phase II trial studies how well veliparib or pembrolizumab work with combination chemotherapy and radiation therapy in treating patients w
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 ...
Background: Endothelin-1 and Endostar are both significant for the progression, proliferation, metastasisand invasion of cancer. In this paper, we studied the effect of ET-1 RNAi and Endostar in PC-3 prostatic cancercells. Materials and Methods: The lentiviral vector was used in the establishment of ET-1 knockdown PC-3 cells.Progression and apoptosis were assessed by CKK-8 and flow cytometry, respectively. Transwell assay was usedto estimate invasion and signaling pathways were studied by Western blotting. Results: ET-1 mRNA and proteinin ET-1 knockdown PC-3 cells were reduced to 26.4% and 22.4% compared with control group, respectively.ET-1 RNAi and Endostar both were effective for the suppression of progression and invasion of PC-3 cells.From Western blotting results, the effects of ET-1 regulation and Endostar on PC-3 cells were at least relatedto some signaling pathways involving PI3K/Akt/Caspase-3, Erk1/2/Bcl-2/Caspase-3 and MMPs (MMP-2 andMMP-9). Furthermore, combined treatment of ET-1RNAi and
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 ...
OncologyPRO is the home of ESMOs educational & scientific resources, with exclusive content for ESMO members such as ESMOs Congresses webcasts,
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
Values were reported as mean ± standard. error of mean (SEM). Statistical significance was set as P < 0.05. Ang II injection induced a slight but consistent constriction in isolated Veliparib mesenteric venules (Fig. 1A). No significant differences were observed between the responses of Wistar rats (10.6 ± 1.1 mmHg; n = 6) and SHR (10.6 ± 1.3 mmHg; n = 8). Basal perfusion pressure in mesenteric venous bed was not modified by pre-incubation with different antagonists. In SHR preparations, the constriction induced by Ang II was nearly abolished (P < 0.05) by perfusion with losartan (0.8 ± 0.2 mmHg; n = 7), while PD123319 and L-NAME had no effect at all. In contrast, Ang II venoconstriction increased (P < 0.05) after B2R blockade with HOE 140 (15.7 ± 1.6 mmHg; n = 8), and also after COX inhibition with indomethacin (16.8 ± 1.5 mmHg,. n = 6) or celecoxib (18.8 ± 1.4 mmHg, n = 5). The results are shown in Fig. 1B. Starting at 1 nmol/L, Ang II contracted rings of portal vein in a ...
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 ...
CrossRef 15. Iwasaki H, Mizokawa Y, Nishitani R, Nakamura S: X-ray photoemission study of the initial Veliparib concentration oxidation of the cleaved (110) surfaces of GaAs, GaP and InSb. Surf Sci 1979, 86:811-818.CrossRef 16. Legare P, Hilaire L, Maire G: The superficial oxidation of indium,. Sb and InSb(111) - a LEED, AES, XPS and UPS study. J Microsc Spectrosc Electron 1980, 5:771-782. 17. Tang X, Weltenis RGV, Setten FMV, Bosch AJ: Oxidation of the InSb surface at room temperature. Semicond Sci Technol 1986, 1:355-365.CrossRef 18. Barr TL, Ying M, Varma SJ: Detailed X-ray photoelectron-spectroscopy valence band and core level studies of select metals oxidations. Vac Sci Technol A 1992, 10:2383-2390.CrossRef 19. Ohshita M: High electron mobility InSb films prepared by source-temperature-programed evaporation method. Jpn J Appl Phys 1971, 10:1365-1371.CrossRef 20. Jin YJ, Zhang DH, Chen XZ, Tang XH: Sb antisite Doramapimod chemical structure defects in InSb epilayers prepared by metalorganic ...
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 ...
Metronomic) Cyclophosphamide Versus Chemotherapy Alone in Patients With Non-Small Cell Lung Adenocarcinoma After Failure of Two ... Dose-escalation Study to Evaluate the Safety and Immunologic Response After Administration of HS-130 in Combination With HS-110 ...
... has been granted orphan drug designation by the US Food and Drug Administration (FDA) and the European Medicines ... Clinical trial number NCT02942264 for "Zotiraciclib (TG02) Plus Dose-Dense or Metronomic Temozolomide Followed by Randomized ... dose-finding study examining zotiraciclib plus dose-dense or metronomic temozolomide (TMZ) in adults with recurrent anaplastic ...
The use of leuprorelin in women of reproductive age before administration of intermittently dosed cyclophosphamide may diminish ... maintenance and metronomic chemotherapy. Cyclophosphamide decreases the immune system's response, and although concerns about ...
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, and was strengthened through truth-telling and following the ... the Zoroastrians were left with no choice but to either conform or migrate to regions that had a more amicable administration. ...
2018). "Successful Second-Line Metronomic Temozolomide in Metastatic Paraganglioma: Case Reports and Review of the Literature ... with continued administration. However, CVD is not the only proven chemotherapeutic regimen in the pheochromocytoma patient. A ... patient's will present to their testing site for a baseline metanephrines blood draw and clonidine administration. They will ... intravenous hydrocortisone in the operating room prior to anesthesia Repeat administration of 25-50 mg intravenous ...
Metronomic" by people in this website by year, and whether "Administration, Metronomic" was a major or minor topic of these ... "Administration, Metronomic" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ... Below are the most recent publications written about "Administration, Metronomic" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Administration, Metronomic". ...
Antineoplastic Agents, Alkylating / administration & dosage * Antineoplastic Agents, Alkylating / therapeutic use * Breast ... Metronomic cyclophosphamide treatment in metastasized breast cancer patients: immunological effects and clinical outcome Cancer ... Over a period of 3 months, we investigated the effect of metronomic low-dose cyclophosphamide on Treg numbers, suppressive ... We conclude that metronomic low-dose cyclophosphamide only transiently reduces Treg but induces stable tumor-specific T-cell ...
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. * ...
This work sheds light on the potential use of metronomic CTX for the treatment of breast cancer, in particular using the quasi- ... Here we report results regarding the use of an immunostimulatory regimen of metronomic cyclophosphamide (CTX). We show that in ... Some have argued that the currently used regimen of CTX administration, i.e., MTD or indeed the 50 mg daily oral metronomic ... Another schedule of metronomic-like CTX, developed by Waxman and colleagues17,18,19,20,21, consisting of 140 mg/kg administered ...
Background: The current study was designed to evaluate the efficacy and toxicity of the continuous oral administration of a ... Metronomic therapy with cyclophosphamide and dexamethasone for prostate carcinoma Cancer. 2003 Oct 15;98(8):1643-8. doi: ...
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 ...
Whereas metronomic administration of CTX caused significant reduction in CTL numbers in the blood immediately after initiation ... We show that the combination of metronomic administration of CTX with immunization provides antitumor responses that are ... Immunotherapy could be initiated well before metronomic dose CTX administration to minimize immunosuppression. With the first ... "metronomic" schedule (10 , 11) . Metronomic delivery was suggested to be improved over traditional chemotherapeutic regimes ...
Metronomic dosing and administration of cyclophosphamide (20 mg/kg/d) was given as described previously (46), i.e., daily ... Based on our preliminary results, we chose metronomic cyclophosphamide plus metronomic irinotecan chemotherapy to assess ... Preliminary assessment of combination metronomic chemotherapy regimens. We tested several monotherapy or combination metronomic ... Low-dose metronomic (LDM) irinotecan (10 mg/kg) and LDM cisplatin (1 mg/kg) were given twice a week by i.p. injection. LDM ...
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 ...
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, 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 ...
... 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 ...
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 ...
For patients with HER2 positive disease, concurrent trastuzumab administration was allowed. Concurrent denosumab or ... metronomic eribulin A phase 2 study of low dose metronomic eribulin in metastatic breast cancer. Chalasani P, Liu AJ, Khanjian ... Conclusions: Metronomic weekly low dose eribulin appears to be an active and tolerable regimen with less myelosuppression, ... Methods: A multi-site prospective open-label phase II trial of metronomic dosing of eribulin in patients with MBC has completed ...
Systemic Administration of Metronomic PEX or PF-4/CTF and Chemotherapy.. We then investigated the effect of the metronomic ... PEX or PF-4/CTF was administered daily alone, or in metronomic combination with chemotherapy. Metronomic administration of both ... PEX, surgery followed by metronomic PEX only; Surg+Metr. PEX and CHT, surgery followed by metronomic PEX and metronomic CHT. ... Recurrent tumors treated with daily PEX alone, metronomic PEX alone, or metronomic PEX combined with metronomic chemotherapy ...
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 ...
Carcinoma, Hepatocellular; Administration, Metronomic; Portal vein; Sorafenib; Thrombosis Full Text Links. *. Actions. Cited ... Metronomic chemotherapy (MET) is frequently administered in comparatively low doses as a continuous chemotherapeutic agent. The ... Can metronomic chemotherapy be an alternative to sorafenib in advanced hepatocellular carcinoma? ... A comparative study of sorafenib and metronomic chemotherapy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma ...
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 ...
... 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 ...
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 ...
Metronomic scheduling; MSAT - metronomic scheduling of anticancer treatment; Protracted low-dose chemotherapy Metronomic ... Metronomic chemotherapy was originally defined as the chronic administration of chemotherapeutic drugs at relatively low, ... Anti-angiogenic chemotherapy; Metronomic scheduling; MSAT - metronomic scheduling of anticancer treatment; Protracted low-dose ... Hanahan D, Bergers G, Bergsland E (2000) Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor ...
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 cyclophosphamide increased expression of tumor cell-derived DNA damage, cell stress, and cell death genes, which may ... Untreated and metronomic cyclophosphamide-treated human U251 glioblastoma xenografts were analyzed on human microarrays at two ... These factors may include useful biomarkers that facilitate discovery of clinically effective immunogenic metronomic drugs and ... However, little is known about the underlying mechanisms whereby metronomic cyclophosphamide induces innate immune cell ...
They would also allow frequent, even daily, dosing (metronomic administration) for a steady effect over time. ... For example, docetaxel administration in a mouse model selectively decreased MDSCs while increasing CTL responses (Kodumudi et ... Metronomic chemotherapy enhances antitumor effects of cancer vaccine by depleting regulatory T lymphocytes and inhibiting tumor ... These two analyses focused on the treatment benefit derived from the administration of sipuleucel-T with or without subsequent ...
  • Recently we experienced three very elderly CRC patients who showed durable response and tolerability to metronomic chemotherapy with oral capecitabine at outpatient clinic. (kjim.org)
  • The present study aimed to evaluate whether capecitabine or 5-fluorouracil (5-Fu) chemotherapy with the metronomic pattern may cause significant chemoresistance compared with the traditional pattern, and whether CAFs are involved in drug resistance. (readbyqxmd.com)
  • and the capecitabine metronomic group (capecitabine LDM group), intragastric administration at 200 mg/kg, twice a week for 6 weeks. (readbyqxmd.com)
  • We describe two cases of unresectable HCC that were treated with low, "metronomic" doses of capecitabine. (kowsarpub.com)
  • Lacking established second-line therapy, metronomic capecitabine may be a valid alternative in the treatment of HCC patients who are judged not eligible for sorafenib or those having progression disease on sorafenib. (kowsarpub.com)
  • We describe two cases of unresectable advanced HCC referred at the Department of Medical and Surgical Sciences of the University of Bologna who obtained long-lasting objective responses after treatment with metronomic capecitabine. (kowsarpub.com)
  • metronomic capecitabine inhibited angiogenesis, growth of gastric cancer and improved survival with less toxicity. (careacross.com)
  • Given its potential low toxicity, the combination of docetaxel and metronomic capecitabine needs to be evaluated to assess efficacy and tolerability in patients with advanced gastric cancer previously treated with a fluoropyrimidine-based and platinum-based chemotherapy. (careacross.com)
  • In combination with other drugs, the treatment with metronomic capecitabine has proven its efficacy with minimal toxicity in breast cancer, in metastatic renal-cell carcinoma, in advanced adrenocortical carcinoma, in hepatocellular carcinoma, in prostate cancer. (careacross.com)
  • Administration of low doses of a drug or a drug combination over prolonged periods of time usually at a regular interval. (sickkids.ca)
  • Such combination therapy may be most useful when "metronomic" doses of antineoplastic drugs are used, thereby potentially avoiding some of the immunosuppressive effects of these drugs. (aacrjournals.org)
  • Metronomic chemotherapy refers to the frequent, typically daily, administration of cytotoxic drugs at doses that are significantly lower than the maximum-tolerated dose, with no prolonged drug-free breaks. (biomedcentral.com)
  • 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. (bioportfolio.com)
  • Metronomic chemotherapy (MET) is frequently administered in comparatively low doses as a continuous chemotherapeutic agent. (koreamed.org)
  • Metronomic chemotherapy, at a minimally toxic dose and with a frequent schedule, is a potentially novel approach to the control of advanced cancer disease via a different mechanism from maximum tolerable doses chemotherapy. (springer.com)
  • METROmaJX is a Phase 1/2 clinical trial evaluating the tolerability and efficacy of the co-administration of Pexa-Vec with metronomic cyclophosphamide (low doses given with high frequency) in patients with advanced solid tumors (NCT02630368). (pharmiweb.com)
  • Metronomic administration involves giving low doses of the drug at a higher frequency and is known to have an immunomodulating activity. (pharmiweb.com)
  • The prolonged administration of low doses of chemotherapy with a greatly reduced break period between doses has come to be known as metronomic administration. (vin.com)
  • The principal goal of metronomic administration of chemotherapy is reduction or elimination of the break period between doses. (vin.com)
  • Metronomic chemotherapy was originally defined as the chronic administration of chemotherapeutic drugs at relatively low, minimally toxic doses and with no prolonged drug-free breaks. (springer.com)
  • Given the high sensitivity of vascular endothelial cells to chemotherapeutic drugs, it was hypothesized that more frequent administration of these drugs at lower doses would result in a potent inhibition of tumor angiogenesis and would prevent the rapid vascular rebound that often occurs during prolonged drug-free breaks following conventional chemotherapy. (springer.com)
  • The definition of metronomic chemotherapy is variable, but usually refers to the continuous administration of low doses of oral chemotherapy drugs designed to target the endothelial cells lining the blood vessels supplying tumor cells. (petmd.com)
  • Historically, metronomic chemotherapy in veterinary medicine consisted of the combination of low doses of oral cyclophosphamide with a non-steroidal anti-inflammatory drug (Feldene/Piroxicam ®), and in some cases, an antibiotic (Doxycycline). (petmd.com)
  • Metronomic chemotherapy involves the continuous (daily or every other day) oral administration of traditional chemotherapy drugs at much lower doses and without the typical drug-free break. (cat-world.com.au)
  • Secondary objectives are: 1) to identify biologically active doses of activated autologous NK cells plus or minus rhIL15 by monitoring changes in NK cell number, phenotype and function, 2) to assess pharmacokinetics and immunogenicity of rhIL15 in a pediatric population, and 3) assess antitumor effects and changes in FDG-PET following administration of activated NK cells to lymphopenic hosts plus or minus rhIL15. (knowcancer.com)
  • The definition of metronomic chemotherapy varies, but generally it refers to repetitive, low doses of chemotherapy drugs designed to minimize toxicity and target the endothelium or tumor stroma as opposed to targeting the tumor. (veterinarycancer.com)
  • There is a considerable body of evidence that even very low, nontoxic doses of chemotherapy drugs, when delivered frequently for a prolonged period of time (metronomic chemotherapy) can retard tumor blood vessel growth (or angiogensis) by destroying endothelial cells. (veterinarycancer.com)
  • Frequent administration of most cytotoxic agents at low doses is thought to increase their putative antiangiogenic activity. (knowcancer.com)
  • Administration of high doses of pharmaceuticals over short periods of time. (bireme.br)
  • Metronomic chemotherapy is a unique protocol that administers chemotherapeutic agents at relatively low doses, without prolonged drug-free periods. (metronomics.org)
  • A new modality of chemotherapy administration is the metronomic schedule, based on the regular frequent use of lower doses of conventional drugs, proposed as an emerging alternative to conventional chemotherapy. (clinmedjournals.org)
  • However, administration of successive doses resulted in a much delayed return to normal synthesis. (saladgaffe.tk)
  • Metronomic chemotherapy refers to the continuous administration (e.g. daily or every other day) of low doses of chemotherapeutic drugs with few or no rest periods. (ndsr.co.uk)
  • Metronomic (low dose, continuous) chemotherapy is based on the fact that blood vessel endothelial cells are highly sensitive to continuous exposure to low doses of chemotherapeutic drugs 2-7 . (hopevs.com)
  • Metronomic chemotherapy is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. (metronomics.org)
  • This work sheds light on the potential use of metronomic CTX for the treatment of breast cancer, in particular using the quasi-weekly regimen, but also underscores the complexity of the anti-tumor mechanisms and potential to improve immune checkpoint therapy efficacy. (nature.com)
  • The current study was designed to evaluate the efficacy and toxicity of the continuous oral administration of a combination of cyclophosphamide (50 mg/day given in the morning) and dexamethasone (1 mg/day given in the evening) in patients with prostate specific antigen (PSA) progression despite single or multiagent hormone therapy and antiandrogen withdrawal. (nih.gov)
  • We therefore assessed the efficacy of antitumor responses generated by a combination of metronomic dosing of CTX with immunization strategies aimed at eliciting CTLs reactive to recombinant epitopes expressed by the murine melanoma model B16.F10. (aacrjournals.org)
  • CES2-expressing tumors may respond to oral metronomic dosing of LY2334737 as gemcitabine that is generated from both systemic and intracellular cleavage, thereby further enhancing efficacy. (aacrjournals.org)
  • Oral administration permits frequent low dosing, on a "metronomic schedule" that may enhance antitumor efficacy ( 3 , 5 ). (aacrjournals.org)
  • Efficacy of cancer immunotherapy with immune checkpoint antibodies can be diminished with administration of antibiotics, and superior efficacy is observed with the presence of specific gut microbes. (sciencemag.org)
  • Furthermore, the cytostatic continuous action of metronomic administration can overcome drug resistance, assuring efficacy without great toxicity [ 3 ]. (clinmedjournals.org)
  • To determine the maximum tolerated dose (MTD) of CPT-11 administered on days 8 and 22 in combination with a fixed, continuous, and metronomic regimen of TMZ, given in 28-day cycles. (clinicaltrials.gov)
  • Here we report results regarding the use of an immunostimulatory regimen of metronomic cyclophosphamide (CTX). (nature.com)
  • Due to poor tolerance, a subsequent treatment regimen consisted of metronomic chemotherapy with chlorambucil combined with an alternative/complementary regimen of I'm-Yunity (polysaccharopeptide) and Yunnan Baiyao. (hindawi.com)
  • Conclusions: Metronomic weekly low dose eribulin appears to be an active and tolerable regimen with less myelosuppression, alopecia and peripheral neuropathy than is seen with approved dose, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen. (her2support.org)
  • A metronomic "chemo-switch" regimen of cyclophosphamide and etoposide may also have activity in canine hemangiosarcoma. (vin.com)
  • 6. Coleman M, Ruan J, Furman RR, Niesvizky R, Martin P, Leonard JP: Oral combination chemotherapy for refractory / relapsed lymphoma with the PEP-C (C3) regimen (daily prednisone, etoposide, procarbazine, cyclophosphamide): low dose continuous metronomic multidrug therapy. (aahpm.org)
  • In the comparator arm, the 5-year progression-free survival improved statistically significantly to 70% and overall survival to 75% in 336 patients with estrogen receptor-negative (includes triple-negative subset) breast cancer with use of dose-dense (once every 2 weeks) administration of doxorubicin, cyclophosphamide, and paclitaxel-a third generation regimen (23% hazard reduction). (medicdebate.org)
  • The objective of the study was to describe response and tolerability of metronomic chemotherapy regimen GFIP/BDC, a modification of the G-FLIP regimen, in patients with persistent or recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer. (biomedcentral.com)
  • 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. (metronomics.org)
  • Furthermore, another topoisomerase 1 inhibitor, irinotecan, when combined with gemcitabine, has been reported to be active when administered in a metronomic fashion in a preclinical model of human colorectal carcinoma xenografts ( 36 ) and lung carcinoma xenografts ( 37 ), and some preliminary clinical data also indicate metronomic irinotecan may be active in human colorectal carcinoma ( 38 ). (aacrjournals.org)
  • The list of chemotherapy agents that may have utility when administered in a metronomic fashion likely extends beyond alkylating agents. (vin.com)
  • A recent phase III clinical trial in high-risk pediatric rhabdomyosarcoma patients showed improved survival when vinorelbine and continuous daily low-dose metronomic CTX was used as maintenance therapy after effective induction therapy, leading to this protocol being adopted as a new standard of care for this indication 6 . (nature.com)
  • The antiangiogenic effects of low-dose continuous metronomic chemotherapy are thought to be mediated through several possible mechanisms, including direct targeting of activated endothelial cells of angiogenic blood vessel capillaries ( 1 , 2 ), and circulating bone marrow-derived endothelial progenitor cells ( 8 , 9 ). (aacrjournals.org)
  • Metronomic chemotherapy, namely administration of continuous low-dose chemotherapy at close, regular intervals, with no prolonged drug-free interruptions, bases its rationale on the fact that virtually all classes of cancer chemotherapeutic drugs are designed to damage DNA or disrupt microtubules of dividing cells. (knowcancer.com)
  • 4 A parallel phase III neoadjuvant study demonstrated a pathologic complete response of 43% with denser doxorubicin (weekly) and cyclophosphamide (continuous) compared with 26% with once-every-3-weeks doxorubicin and cyclophosphamide, both arms receiving weekly paclitaxel in locally advanced breast cancer, suggesting an additive benefit of denser administration doxorubicin and cyclophosphamide, in addition to the denser administration of paclitaxel. (medicdebate.org)
  • Since its inception, several other drugs have been examined as metronomic therapy, including veterinary approved non-steroidal anti-inflammatory drugs (e.g. (petmd.com)
  • However, there is recent interest in treatment with metronomic cyclophosphamide and piroxicam for prevention of tumour regrowth in dogs with dirty surgical margins and no other ancillary therapy. (vin.com)
  • Metronomic chemotherapy is usually associated with better tolerance than conventional chemotherapy, and encouraging response rates have been reported in various settings. (nih.gov)
  • It is by essence opposed to conventional chemotherapy, which is based on the administration of chemotherapy drugs slightly below or at the maximum-tolerated dose every 2 or 3 weeks. (springer.com)
  • Pages 3-21 The concept of metronomic dosing and scheduling of conventional chemotherapy drugs was first published in 2000, based on preclinical findings. (metronomics.org)
  • High-frequency low-dose (also known as metronomic) chemotherapy can help improve the activity of CTLs by providing sufficient stimulation for cytotoxic immune cells without excessive depletion. (mdpi.com)
  • 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)
  • This book coversall aspects of metronomic chemotherapy, describes the pharmacological bases of metronomic chemotherapy, presents and discusses the clinical results of all published studies on metronomic chemotherapy, in a wide range of tumors This book analyzes all aspects of metronomic chemotherapy, a new approach involving low-dose, long-term, and frequently administered therapy that has preclinical and clinical activity in various tumors. (metronomics.org)
  • Clinical applications of metronomic chemotherapy in a wide variety of tumors are then addressed in detail, with description of the results of all published studies. (metronomics.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)
  • Low-dose metronomic chemotherapy represents a new strategy to treat solid tumors by exhibiting stronger anti-angiogenic activity and less side effects, especially in combination with other anti-angiogenic agents. (careacross.com)
  • Taking advantage of the potential effectiveness of metronomic therapy, tegafur/uracil (UFT) was incorporated into an oxaliplation/infusioanl fluouracil (5-FU)/leucovorin (LV) protocol in this study. (springer.com)
  • OBJECTIVE To determine the effectiveness of metronomic cyclophosphamide (MC) chemotherapy (primary treatment of interest) with adjuvant meloxicam administration as maintenance treatment for dogs with appendicular osteosarcoma following limb amputation and carboplatin chemotherapy. (tripawds.com)
  • Despite this, metronomic gemcitabine significantly inhibited tumor angiogenesis and reduced tumor perfusion and inflammation in vivo , while standard gemcitabine did not. (nih.gov)
  • Not all metronomic chemotherapy drugs and regimens are likely to be equally efficacious, despite the fact that sustained angiogenesis and immune evasion are general hallmarks of tumour growth. (vin.com)
  • Hanahan D, Bergers G, Bergsland E (2000) Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. (springer.com)
  • Metronomic chemotherapy is one example of angiogenesis inhibition treatment, which is becoming a popular treatment option for pets with cancer. (petmd.com)
  • Metronomic chemotherapy was primarily developed to target circulating endothelial progenitor cells to inhibit tumor angiogenesis. (metronomics.org)
  • Metronomic chemotherapy using off-patent drugs such as CTX offers potential clinical benefits such as causing less toxicity compared to maximum tolerated dose (MTD) regimens, acting as an immunostimulatory therapy in some cases and being more economically viable especially for use in long-term maintenance therapy settings 4 , 5 . (nature.com)
  • Effects of low-dose CTX therapy on cellular components of the immune system have long been known and it has been used as an upfront therapy prior to administration of a tumor vaccine or adoptive immune cell transfer 7 , 8 . (nature.com)
  • We therefore investigated whether such metronomic therapy with the alkylating agent cyclophosphamide (CTX) could be effectively combined with immunotherapy eliciting tumor-reactive CTLs. (aacrjournals.org)
  • The combination of immunotherapy and metronomic CTX therapy may be well suited to clinical management of cancer. (aacrjournals.org)
  • Concurrent combination of metronomic chemotherapy with targeted biological antiangiogenic agents such as anti-VEGF receptor 2 (VEGFR-2) antibodies or small molecule receptor tyrosine kinase inhibitors can sometimes cause surprisingly potent and sustained antitumor effects in preclinical models, accompanied by an absence of overt host toxicity even after chronic therapy ( 1 , 2 , 15 ). (aacrjournals.org)
  • An oral version of topotecan has been approved ( 33 ) and thus, in theory, would be ideal for metronomic chemotherapy regimens involving prolonged daily therapy, similar to oral cyclophosphamide. (aacrjournals.org)
  • For your reference, here are all of the posts my pawrents wrote about when I was on Metronomic Therapy. (tripawds.com)
  • Here's a great look at the latest in metronomic therapy by our favorite vet, Dr. Pam Wiltzius. (tripawds.com)
  • N. André , L. Padovani and E. Pasquier , Metronomic scheduling of anticancer treatment: The next generation of multitarget therapy? (aimsciences.org)
  • A new and promising therapy in the treatment of cancer is metronomic chemotherapy. (cat-world.com.au)
  • Biologic (anti-neoplastic agent) or metronomic non-myelosuppressive chemotherapy: At least 7 days must have elapsed since the completion of therapy with a biologic agent. (knowcancer.com)
  • A fundamental principle is to avoid high dose chemotherapy and utilize low dose metronomic, albumin-based chemo combination therapy with NK and T cell immuno-stimulatory fusion proteins. (pharmiweb.com)
  • In veterinary medicine, there have been several studies published that give promise to the principle of metronomic or anti-angiogenic therapy. (veterinarycancer.com)
  • Dr. Robert Kerbel (Toronto, Ontario) is one of the leaders in anti-angiogenic and metronomic therapy. (veterinarycancer.com)
  • Therefore, at the Animal Cancer and Imaging Center, we recommend standard MTD chemotherapy combined with low dose metronomic therapy for many tumor types such as osteosarcoma and hemangiosarcoma. (veterinarycancer.com)
  • For other tumor types, metronomic chemotherapy may be the primary modality of therapy or will start after standard therapy has ended. (veterinarycancer.com)
  • 5) Another protocol, PEPC, used Procarbazine in place of CCNU and was administered as metronomic therapy. (aahpm.org)
  • Most promising applications of metronomic chemotherapy may be in the maintenance treatment setting after induction therapy, using oral chemotherapeutic drugs, especially when combined with certain types of targeted agents such as VEGF pathway inhibiting antiangiogenic agents. (metronomics.org)
  • In our experience we have chosen to treat 41 elderly patients with advanced NSCLC with metronomic chemotherapy in first line, independently from their tumor histology, with the principal aim to preserve their QoL by reducing therapy toxicity. (clinmedjournals.org)
  • No significant change was detected in other angiogenic markers or in Treg numbers.The results presented here indicate that maintenance therapy in children with ALL exerts its antitumor activity at least in part through anti-angiogenic effects, similar to those induced by metronomic chemotherapy. (crcm-marseille.fr)
  • For these reasons, the development of reliable methods (for example) and metronomic therapy to prevent relapse at locally advanced setting may improve the outcome of treatment. (careacross.com)
  • A metronomic therapy [ 4 ] with oral weekly vinorelbine, daily celecoxib and daily valproic acid was then started and lasted until February 2015 (13 months), when new tumour progression was observed. (ecancer.org)
  • Over a period of 3 months, we investigated the effect of metronomic low-dose cyclophosphamide on Treg numbers, suppressive capacity and proliferation on endogenous anti-tumor T-cell responses and on their correlation to clinical outcome in 12 patients with treatment-refractory metastasized breast cancer who received single-agent 50 mg cyclophosphamide p.o. daily. (nih.gov)
  • Combining this immunotherapeutic regime with metronomic delivery of CTX resulted in antitumor activity that was dramatically enhanced over either treatment administered alone and was also significantly greater than combining immunotherapy with CTX administered by a maximum tolerated dose regime. (aacrjournals.org)
  • Further analysis showed that metronomic CTX treatment did not delete cells with low expression of CD43, a "memory" phenotype, and that these cells maintained potent restimulatory capacity. (aacrjournals.org)
  • We hypothesized that a low dose metronomic schedule will allow responding patients to remain on treatment, resulting in longer TTP (time to progression) and decreased incidence of toxicities and treatment-related discontinuations. (her2support.org)
  • My vet who works with Dr. Rosenberg said that she is using the metronomic on dogs more and more now to fight cancer because it's proving to be a very effective chemo treatment. (tripawds.com)
  • New Drug Administration Option Improves Treatment Success and Decreases Side Effects. (tripawds.com)
  • Cyclophosphamide treatment on a six-day repeating metronomic schedule induces a dramatic, innate immune cell-dependent regression of implanted gliomas. (biomedcentral.com)
  • 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. (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)
  • Because intact prodrug circulates at high plasma levels after oral LY2334737 administration, improved response rates may be observed by tailoring LY2334737 treatment to patients with CES2 tumor expression. (aacrjournals.org)
  • Chemotherapy drugs are poorly absorbed, but this treatment allows for better penetration by delivering electric impulsions into the tumour after administration of chemotherapy. (cat-world.com.au)
  • In particular, monoclonal antibodies (mAbs) that block the engagement of the inhibitory receptor PD-1 by its main ligand PD-L1 have to date been approved by the U.S. Food and Drug Administration (FDA) for use in the treatment of patients with 10 distinct tumor types ( 1 ). (sciencemag.org)
  • a genetically modified adenovirus) was approved for commercialization and routine application in the treatment of nasopharyngeal carcinoma, by the Chinese State Food and Drug Administration (FDA) ( 9 ). (jcancer.org)
  • Used with disease headings for the treatment of disease by the administration of drugs, chemicals, and antibiotics. (bireme.br)
  • Earlier this month, Tanovea-CA1 received conditional approval from the Food and Drug Administration for treatment of dogs with lymphoma. (o-cockaigne.eu)
  • This relatively new treatment strategy concept is called low-dose metronomic (LDM) chemotherapy. (metronomics.org)
  • Zotiraciclib has been granted orphan drug designation by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of gliomas. (wikipedia.org)
  • These results suggest that metronomic chemotherapy can be an effective choice of treatment for elderly NSCLC patients and further trials with more patients are needed to confirm this proposal. (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)
  • A different treatment approach using metronomic administration of chemotherapy has thus emerged in recent years as an alternative. (biomedcentral.com)
  • We conclude that metronomic low-dose cyclophosphamide only transiently reduces Treg but induces stable tumor-specific T-cell responses, which correlate with improved clinical outcome in advanced-stage breast cancer patients. (nih.gov)
  • However, because bevacizumab monotherapy is known to be active in advanced ovarian cancer ( 23 - 28 ), it is not clear whether the addition of the metronomic cyclophosphamide contributed meaningful additional activity to the observed clinical benefits in these trials. (aacrjournals.org)
  • 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. (unicampania.it)
  • However, additional clinical pharmacology and clinical trial data are needed to further support the use of a complementary/holistic approach in combination with metronomic chemotherapy. (hindawi.com)
  • However, the clinical benefit had to be weighted in regards of the inconvenience of returning to clinic weekly for administration of the drug. (biomedcentral.com)
  • However, clinical development of metronomic chemotherapy has been hampered by a number of limitations, including the vagueness of its definition and the resulting empiricism in protocol design. (nih.gov)
  • It must be kept in mind that the laboratory and clinical research with metronomic chemotherapy administration is ongoing but extremely promising. (veterinarycancer.com)
  • The clinical pharmacology of metronomic chemotherapy is also considered in depth, encompassing pharmacokinetics, pharmacogenetics, pharmacoenconomics, and adverse drug reactions. (metronomics.org)
  • The first Phase 1b clinical trial of zotiraciclib in GBM, sponsored by the National Cancer Institute (NCI), is a multi-arm, dose-finding study examining zotiraciclib plus dose-dense or metronomic temozolomide (TMZ) in adults with recurrent anaplastic astrocytoma and GBM. (wikipedia.org)
  • However, the clinical use of TP for AD could be hampered due to its high toxicity, instability, poor water solubility, and nonspecific biodistribution after administration. (bvsalud.org)
  • Low-dose daily metronomic cyclophosphamide (LDM CTX) has been shown to reduce numbers of regulatory T cells (T regs ) preclinically and in patients 9 , 10 . (nature.com)
  • Low dose daily metronomic dosing has shown promise in terms of improved therapeutic activity and reduced host toxicity compared to maximum tolerated dose chemotherapy, however, large randomized trials are required to definitively establish its therapeutic advantages. (biomedcentral.com)
  • The ability to provide frequent administration, most often necessitating oral dosing, is a key component to drug suitability. (vin.com)
  • In children with cancer, celecoxib has been used in combination with chemotherapy in metronomic (lower dose but more frequent administration) regimens. (anticancerfund.org)
  • Metronomic cyclophosphamide with piroxicam has been shown to delay or prevent the regrowth of incompletely excised canine soft tissue sarcomas. (vin.com)
  • 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)
  • It involves the close, regular administration of conventional chemotherapeutic drugs without prolonged drug-free "holidays" over extended periods of time ( 1 - 3 ). (aacrjournals.org)
  • Combining immune checkpoint inhibition with metronomic administration of chemotherapeutic drugs may create a synergistic effect that augments anti-tumor immune responses and clears metabolic competition. (mdpi.com)
  • In this study, we developed a pharmacokinetic/pharmacodynamic mathematical model that identifies in silico the most effective administration schedule for gemcitabine monotherapy. (nih.gov)
  • Systemic exposure to gemcitabine was 14 times lower in the metronomic groups compared with the standard group. (nih.gov)
  • A prodrug of gemcitabine, LY2334737, was prepared that alters the properties of gemcitabine to allow oral administration and improved stability ( Fig. 1 ). (aacrjournals.org)
  • 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)
  • Of the many cytotoxic chemotherapy drugs available, prolonged administration of alkylating agents, such as cyclophosphamide, chlorambucil, and lomustine have arguably received the most investigation. (vin.com)
  • The objective of this study was to investigate a possible mechanism of action of metronomic chlorambucil on glioma by studying the in vitro cytotoxicity and anti-angiogenic effects on glioma and endot. (bioportfolio.com)
  • The primary aim of this trial was to determine the recommended phase II dose (RP2D) of weekly paclitaxel (wP) administered in combination with oral metronomic cyclophosphamide (OMC). (biomedcentral.com)
  • It relies on the long-term oral administration of daily low-dose mercaptopurin and weekly low-dose methotrexate. (crcm-marseille.fr)
  • In principle, one such combination is low or lower dose metronomic chemotherapy, in particular known immunostimulatory regimens of metronomic cyclophosphamide (CTX). (nature.com)
  • We show that the combination of metronomic administration of CTX with immunization provides antitumor responses that are dramatically enhanced over immunotherapy or chemotherapy alone and that are also enhanced over immunotherapy combined with CTX administered at the MTD. (aacrjournals.org)
  • Metronomic administration of zoledronic acid and taxotere combination in castration resistant prostate cancer patients: phase I ZANTE trial. (unicampania.it)
  • We hypothesize that metronomic cyclophosphamide and weekly paclitaxel combination is feasible combination. (biomedcentral.com)
  • In this context, we performed a multi-center dose-finding phase I trial to determine the recommended phase II dose of weekly paclitaxel administered in combination with metronomic cyclophosphamide and to evaluate the safety and preliminary signs of activity of this combination. (biomedcentral.com)
  • As inhibitors we used PEX and a fragment of platelet factor 4 (PF-4/CTF), which were administered systemically on a daily basis or in metronomic combination with chemotherapy for 120 days. (aacrjournals.org)
  • She was initially treated with metronomic temozolomide (50 mg/m 2 /day) in combination with radiotherapy (54 Gy) with subsequent monthly courses of temozolomide 200 mg/m 2 for 5 days every 4 weeks [ 2 ]. (ecancer.org)
  • Metronomic delivery was suggested to be improved over traditional chemotherapeutic regimes involving MTD because the latter require extended rest periods to allow the patient to recover from associated toxicity, a respite that also provides time for the endothelial compartment within tumor tissue to repair. (aacrjournals.org)
  • Metronomic chemotherapy, continuously low dose administration of chemotherapeutic agents, has been reported to have a low toxicity and anticancer effect. (kjim.org)
  • Toxicity might be a limiting factor for administration. (biomedcentral.com)
  • Whereas both metronomic and maximum tolerated dose delivery of CTX did cause deletion of proliferating tumor-specific CTLs in the blood, this deletion occurred with slower kinetics with the metronomic schedule. (aacrjournals.org)
  • In contrast to conventional, pulsatile maximum tolerated dose (MTD) chemotherapy, the main primary target, initially, of metronomic chemotherapy is thought to be the tumor's neovasculature ( 1 - 3 ), although additional mechanisms are likely involved as well, e.g., stimulation of the immune system through reduction in regulatory T cells ( 4 - 6 ) and possibly direct tumor cell-targeting effects ( 7 ). (aacrjournals.org)
  • Preliminary studies of metronomic schedules with each of these drugs have been reported. (vin.com)
  • 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)
  • their inhibition may contribute to the therapeutic effectiveness of the six-day repeating metronomic cyclophosphamide schedule. (biomedcentral.com)
  • Key upstream regulators activated by metronomic cyclophosphamide include members of the interferon, toll-like receptor, inflammatory response, and PPAR signaling pathways, whose activation may contribute to anti-tumor immunity. (biomedcentral.com)
  • Low-dose metronomic cyclophosphamide complements the actions of an intratumoral C-class CpG TLR9 agonist to potentiate innate immunity and drive potent T. (oncotarget.com)
  • After an opening section on the pharmacological bases of metronomic chemotherapy, including its antiangiogenic effects and impact on immunity, preclinical studies on various classes of drug are discussed. (metronomics.org)
  • Survival of animals that received daily PEX or PF-4/CTF was similar to that of animals that received metronomic PEX or PF-4/CTF and chemotherapy, respectively. (aacrjournals.org)
  • J Vet Intern Med 2007;21(4):764-9] showed that in patients with hemangiosarcoma, the use of metronomic chemotherapy was associated with survival times equal to that of MTD chemotherapy. (veterinarycancer.com)
  • 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. (biomedcentral.com)
  • Even if it did, there may be better chemotherapy drugs for metronomic chemotherapy-based treatments of ovarian cancer. (aacrjournals.org)
  • We used β-hCG-tagged mouse B16 melanoma and erbB-2/Her-2-expressing human breast cancer MDA-MB-231 models, and drug treatments included metronomic low-dose cyclophosphamide chemotherapy with or without a vascular endothelial growth factor receptor 2-targeting antibody (DC101) or trastuzumab, the erbB-2/Her-2-targeting antibody. (aacrjournals.org)
  • This paradigm change holds the potential to coordinate NK and T cells responses while inducing ICD with metronomic chemo-radiation, and a common cancer vaccine for all tumor types regardless of anatomical origin. (pharmiweb.com)
  • The novel approach of this Cancer Memory Vaccine is to activate the patient's own NK cells with fusion proteins, supplemented by administration of off-the-shelf tumor targeted NK cell infusions, combined with inducing neoantigen and tumor associated antigen-specific memory T cells using adenovirus and yeast vaccines. (pharmiweb.com)
  • The anthracycline class of chemotherapeutics - doxorubicin (Adriamycin), daunorubicin, epirubicin, idarubicin - have been used for four decades to treat many types of cancer, including leukemia, lymphoma, sarcomas and carcinomas, The standard method of administration had been to use the highest tolerable dose every few weeks to kill all rapidly growing cells by preventing them from accurately copying their genetic material. (hopkinsmedicine.org)
  • Kerbel RS and Kamen BA, The Anti-Angiogenic Basis of Metronomic Chemotherapy, Nature Reviews Cancer 2004. (veterinarycancer.com)
  • A personal account of the historical development of the metronomic chemotherapy concept is summarized along with suggestions for improving its impact as a promising means of achieving better and less toxic cancer control, not only in patients in low and middle income countries, but also patients in highly developed high income countries as well. (metronomics.org)
  • In this respect, a new approach to the administration of anti-cancer drugs, metronomic chemotherapy, has proven very successful. (ndsr.co.uk)
  • The "metronomic" strategy was also considered in pretreated elderly patients with advanced gastric cancer. (careacross.com)
  • The low cost, ease of administration, and generally well-tolerated adverse event profile has made metronomic administration of chemotherapy drugs appealing in veterinary oncology. (vin.com)
  • This model is based upon four biological assumptions regarding the mechanisms of action of metronomic chemotherapy, resulting in a set of 6 minimally parameterized differential equations. (nih.gov)
  • Pasquier E., André N. (2014) Metronomic Chemotherapy. (springer.com)