Receptor, Serotonin, 5-HT2A: A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD.Receptor, Serotonin, 5-HT1A: A serotonin receptor subtype found distributed through the CENTRAL NERVOUS SYSTEM where they are involved in neuroendocrine regulation of ACTH secretion. The fact that this serotonin receptor subtype is particularly sensitive to SEROTONIN RECEPTOR AGONISTS such as BUSPIRONE suggests its role in the modulation of ANXIETY and DEPRESSION.Receptors, Serotonin, 5-HT1: A subclass of G-protein coupled SEROTONIN receptors that couple preferentially to GI-GO G-PROTEINS resulting in decreased intracellular CYCLIC AMP levels.Receptors, Serotonin, 5-HT3: A subclass of serotonin receptors that form cation channels and mediate signal transduction by depolarizing the cell membrane. The cation channels are formed from 5 receptor subunits. When stimulated the receptors allow the selective passage of SODIUM; POTASSIUM; and CALCIUM.Receptor, Serotonin, 5-HT1B: A serotonin receptor subtype found at high levels in the BASAL GANGLIA and the frontal cortex. It plays a role as a terminal autoreceptor that regulates the rate of SEROTONIN release from nerve endings. This serotonin receptor subtype is closely related to and has similar drug binding properties as the 5-HT1D RECEPTOR. It is particularly sensitive to the agonist SUMATRIPTAN and may be involved in mediating the drug's antimigraine effect.Receptor, Serotonin, 5-HT2C: A serotonin receptor subtype found primarily in the CENTRAL NERVOUS SYSTEM and the CHOROID PLEXUS. This receptor subtype is believed to mediate the anorectic action of SEROTONIN, while selective antagonists of the 5-HT2C receptor appear to induce ANXIETY. Several isoforms of this receptor subtype exist, due to adenine deaminase editing of the receptor mRNA.Serotonin 5-HT2 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes.Serotonin 5-HT1 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT1 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT1 receptor subtypes.HT29 Cells: Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Serotonin 5-HT2 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT2 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT2 receptor subtypes.Receptors, Serotonin: Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.Receptor, Serotonin, 5-HT1D: A serotonin receptor subtype that is localized to the CAUDATE NUCLEUS; PUTAMEN; the NUCLEUS ACCUMBENS; the HIPPOCAMPUS, and the RAPHE NUCLEI. It plays a role as a terminal autoreceptor that regulates the rate of SEROTONIN release from nerve endings. This serotonin receptor subtype is closely related to and has similar drug binding properties as the 5-HT1B RECEPTOR, but is expressed at low levels. It is particularly sensitive to the agonist SUMATRIPTAN and may be involved in mediating the drug's antimigrane effect.Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Serotonin 5-HT3 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.Serotonin 5-HT1 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT1 RECEPTORS, thereby blocking the actions of SEROTONIN 5-HT1 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more of the specific 5-HT1 receptor subtypes.ATP Binding Cassette Transporter 1: A superfamily of large integral ATP-binding cassette membrane proteins whose expression pattern is consistent with a role in lipid (cholesterol) efflux. It is implicated in TANGIER DISEASE characterized by accumulation of cholesteryl ester in various tissues.Serotonin Receptor Agonists: Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.P-Glycoprotein: A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).Biological Transport, Active: The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy.Multidrug Resistance-Associated Proteins: A sequence-related subfamily of ATP-BINDING CASSETTE TRANSPORTERS that actively transport organic substrates. Although considered organic anion transporters, a subset of proteins in this family have also been shown to convey drug resistance to neutral organic drugs. Their cellular function may have clinical significance for CHEMOTHERAPY in that they transport a variety of ANTINEOPLASTIC AGENTS. Overexpression of proteins in this class by NEOPLASMS is considered a possible mechanism in the development of multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although similar in function to P-GLYCOPROTEINS, the proteins in this class share little sequence homology to the p-glycoprotein family of proteins.Serotonin 5-HT3 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT3 RECEPTORS.Serotonin 5-HT4 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT4 RECEPTORS.Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Apolipoprotein A-I: The most abundant protein component of HIGH DENSITY LIPOPROTEINS or HDL. This protein serves as an acceptor for CHOLESTEROL released from cells thus promoting efflux of cholesterol to HDL then to the LIVER for excretion from the body (reverse cholesterol transport). It also acts as a cofactor for LECITHIN CHOLESTEROL ACYLTRANSFERASE that forms CHOLESTEROL ESTERS on the HDL particles. Mutations of this gene APOA1 cause HDL deficiency, such as in FAMILIAL ALPHA LIPOPROTEIN DEFICIENCY DISEASE and in some patients with TANGIER DISEASE.Drug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.Serotonin 5-HT4 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT4 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN RECEPTOR AGONISTS.8-Hydroxy-2-(di-n-propylamino)tetralin: A serotonin 1A-receptor agonist that is used experimentally to test the effects of serotonin.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Rubidium: An element that is an alkali metal. It has an atomic symbol Rb, atomic number 37, and atomic weight 85.47. It is used as a chemical reagent and in the manufacture of photoelectric cells.Ketanserin: A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.P-Glycoproteins: A subfamily of transmembrane proteins from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS that are closely related in sequence to P-GLYCOPROTEIN. When overexpressed, they function as ATP-dependent efflux pumps able to extrude lipophilic drugs, especially ANTINEOPLASTIC AGENTS, from cells causing multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although P-Glycoproteins share functional similarities to MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS they are two distinct subclasses of ATP-BINDING CASSETTE TRANSPORTERS, and have little sequence homology.Kinetics: The rate dynamics in chemical or physical systems.Lipoproteins, HDL: A class of lipoproteins of small size (4-13 nm) and dense (greater than 1.063 g/ml) particles. HDL lipoproteins, synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport). Their major protein component is APOLIPOPROTEIN A-I. HDL also shuttle APOLIPOPROTEINS C and APOLIPOPROTEINS E to and from triglyceride-rich lipoproteins during their catabolism. HDL plasma level has been inversely correlated with the risk of cardiovascular diseases.Ethidium: A trypanocidal agent and possible antiviral agent that is widely used in experimental cell biology and biochemistry. Ethidium has several experimentally useful properties including binding to nucleic acids, noncompetitive inhibition of nicotinic acetylcholine receptors, and fluorescence among others. It is most commonly used as the bromide.Drug Resistance, Multiple, Bacterial: The ability of bacteria to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.Rubidium Radioisotopes: Unstable isotopes of rubidium that decay or disintegrate emitting radiation. Rb atoms with atomic weights 79-84, and 86-95 are radioactive rubidium isotopes.Tangier Disease: An autosomal recessively inherited disorder caused by mutation of ATP-BINDING CASSETTE TRANSPORTERS involved in cellular cholesterol removal (reverse-cholesterol transport). It is characterized by near absence of ALPHA-LIPOPROTEINS (high-density lipoproteins) in blood. The massive tissue deposition of cholesterol esters results in HEPATOMEGALY; SPLENOMEGALY; RETINITIS PIGMENTOSA; large orange tonsils; and often sensory POLYNEUROPATHY. The disorder was first found among inhabitants of Tangier Island in the Chesapeake Bay, MD.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Thoracica: A superorder of marine CRUSTACEA, free swimming in the larval state, but permanently fixed as adults. There are some 800 described species, grouped in several genera, and comprising of two major orders of barnacles: stalked (Pedunculata) and sessile (Sessilia).Bacterial Proteins: Proteins found in any species of bacterium.Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.Sodium Isotopes: Stable sodium atoms that have the same atomic number as the element sodium, but differ in atomic weight. Na-23 is a stable sodium isotope.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Genes, MDR: Genes for MEMBRANE TRANSPORT PROTEINS that confer resistance to toxic compounds. Several superfamilies of these multidrug export proteins are known and found in both prokaryotes and eukaryotes.Calcium Radioisotopes: Unstable isotopes of calcium that decay or disintegrate emitting radiation. Ca atoms with atomic weights 39, 41, 45, 47, 49, and 50 are radioactive calcium isotopes.Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Rhodamine 123: A fluorescent probe with low toxicity which is a potent substrate for P-glycoprotein and the bacterial multidrug efflux transporter. It is used to assess mitochondrial bioenergetics in living cells and to measure the efflux activity of P-glycoprotein in both normal and malignant cells. (Leukemia 1997;11(7):1124-30)Antiporters: Membrane transporters that co-transport two or more dissimilar molecules in the opposite direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is "powered" by the movement of another ion or molecule with its electrochemical gradient.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Drug Resistance, Bacterial: The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Raphe Nuclei: Collections of small neurons centrally scattered among many fibers from the level of the TROCHLEAR NUCLEUS in the midbrain to the hypoglossal area in the MEDULLA OBLONGATA.Potassium Isotopes: Stable potassium atoms that have the same atomic number as the element potassium, but differ in atomic weight. K-41 is a stable potassium isotope.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Serotonin Agents: Drugs used for their effects on serotonergic systems. Among these are drugs that affect serotonin receptors, the life cycle of serotonin, and the survival of serotonergic neurons.Amphetamines: Analogs or derivatives of AMPHETAMINE. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Orphan Nuclear Receptors: A broad category of receptor-like proteins that may play a role in transcriptional-regulation in the CELL NUCLEUS. Many of these proteins are similar in structure to known NUCLEAR RECEPTORS but appear to lack a functional ligand-binding domain, while in other cases the specific ligands have yet to be identified.PiperazinesProbenecid: The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy.Lipoproteins, HDL3: Intermediate-density subclass of the high-density lipoproteins, with particle sizes between 7 to 8 nm. As the larger lighter HDL2 lipoprotein, HDL3 lipoprotein is lipid-rich.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Acriflavine: 3,6-Diamino-10-methylacridinium chloride mixt. with 3,6-acridinediamine. Fluorescent dye used as a local antiseptic and also as a biological stain. It intercalates into nucleic acids thereby inhibiting bacterial and viral replication.Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions.Bacterial Outer Membrane Proteins: Proteins isolated from the outer membrane of Gram-negative bacteria.Caco-2 Cells: Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells, such as ENTEROCYTES. These cells are valuable in vitro tools for studies related to intestinal cell function and differentiation.Blood-Brain Barrier: Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.Scavenger Receptors, Class B: A family of scavenger receptors that are predominately localized to CAVEOLAE of the PLASMA MEMBRANE and bind HIGH DENSITY LIPOPROTEINS.QuinolinesRitanserin: A selective and potent serotonin-2 antagonist that is effective in the treatment of a variety of syndromes related to anxiety and depression. The drug also improves the subjective quality of sleep and decreases portal pressure.Sumatriptan: A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of MIGRAINE DISORDERS.Calcium Isotopes: Stable calcium atoms that have the same atomic number as the element calcium, but differ in atomic weight. Ca-42-44, 46, and 48 are stable calcium isotopes.Indoles: 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.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Cardanolides: The aglycone constituents of CARDIAC GLYCOSIDES. The ring structure is basically a cyclopentanoperhydrophenanthrene nucleus attached to a lactone ring at the C-17 position.4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid: An inhibitor of anion conductance including band 3-mediated anion transport.Tetracycline Resistance: Nonsusceptibility of bacteria to the action of TETRACYCLINE which inhibits aminoacyl-tRNA binding to the 30S ribosomal subunit during protein synthesis.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Methiothepin: A serotonin receptor antagonist in the CENTRAL NERVOUS SYSTEM used as an antipsychotic.Pseudomonas aeruginosa: A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.Lipoproteins: Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Potassium Radioisotopes: Unstable isotopes of potassium that decay or disintegrate emitting radiation. K atoms with atomic weights 37, 38, 40, and 42-45 are radioactive potassium isotopes.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.Drug Resistance, Microbial: The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Fluorescent Dyes: Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.Extracellular Space: Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall.Hydroxyindoleacetic AcidSerotonin Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of serotonergic neurons. They are different than SEROTONIN RECEPTORS, which signal cellular responses to SEROTONIN. They remove SEROTONIN from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. Regulates signal amplitude and duration at serotonergic synapses and is the site of action of the SEROTONIN UPTAKE INHIBITORS.Cyclodextrins: A homologous group of cyclic GLUCANS consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances.High-Density Lipoproteins, Pre-beta: A highly dense subclass of the high-density lipoproteins, with particle sizes below 7 nm. They are also known as nascent HDL, composed of a few APOLIPOPROTEIN A-I molecules which are complexed with PHOSPHOLIPIDS. The lipid-poor pre-beta-HDL particles serve as progenitors of HDL3 and then HDL2 after absorption of free cholesterol from cell membranes, cholesterol esterification, and acquisition of apolipoproteins A-II, Cs, and E. Pre-beta-HDL initiate the reverse cholesterol transport process from cells to liver.Fluoroquinolones: A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.Norfloxacin: A synthetic fluoroquinolone (FLUOROQUINOLONES) with broad-spectrum antibacterial activity against most gram-negative and gram-positive bacteria. Norfloxacin inhibits bacterial DNA GYRASE.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Ion Pumps: A general class of integral membrane proteins that transport ions across a membrane against an electrochemical gradient.Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.Radioisotopes: Isotopes that exhibit radioactivity and undergo radioactive decay. (From Grant & Hackh's Chemical Dictionary, 5th ed & McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.Organic Anion Transporters: Proteins involved in the transport of organic anions. They play an important role in the elimination of a variety of endogenous substances, xenobiotics and their metabolites from the body.Methysergide: An ergot derivative that is a congener of LYSERGIC ACID DIETHYLAMIDE. It antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. Methysergide is used prophylactically in migraine and other vascular headaches and to antagonize serotonin in the carcinoid syndrome.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Valinomycin: A cyclododecadepsipeptide ionophore antibiotic produced by Streptomyces fulvissimus and related to the enniatins. It is composed of 3 moles each of L-valine, D-alpha-hydroxyisovaleric acid, D-valine, and L-lactic acid linked alternately to form a 36-membered ring. (From Merck Index, 11th ed) Valinomycin is a potassium selective ionophore and is commonly used as a tool in biochemical studies.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Pyronine: Xanthene dye used as a bacterial and biological stain. Synonyms: Pyronin; Pyronine G; Pyronine Y. Use also for Pyronine B. which is diethyl-rather than dimethylamino-.Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis.Taurine: A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Dopamine: 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.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.TritiumTetracycline: A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis.Membrane Fusion Proteins: Proteins that catalyze MEMBRANE FUSION.Decapodiformes: A superorder of CEPHALOPODS comprised of squid, cuttlefish, and their relatives. Their distinguishing feature is the modification of their fourth pair of arms into tentacles, resulting in 10 limbs.Tryptamines: Decarboxylated monoamine derivatives of TRYPTOPHAN.4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid: A non-penetrating amino reagent (commonly called SITS) which acts as an inhibitor of anion transport in erythrocytes and other cells.Rhodamines: A family of 3,6-di(substituted-amino)-9-benzoate derivatives of xanthene that are used as dyes and as indicators for various metals; also used as fluorescent tracers in histochemistry.AcridinesEnterobacter aerogenes: Gram-negative, capsulated, gas-producing rods found widely in nature. Both motile and non-motile strains exist. The species is closely related to KLEBSIELLA PNEUMONIAE and is frequently associated with nosocomial infectionsIon Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Serotonin Uptake Inhibitors: Compounds that specifically inhibit the reuptake of serotonin in the brain.5-Hydroxytryptophan: The immediate precursor in the biosynthesis of SEROTONIN from tryptophan. It is used as an antiepileptic and antidepressant.Ruthenium Red: An inorganic dye used in microscopy for differential staining and as a diagnostic reagent. In research this compound is used to study changes in cytoplasmic concentrations of calcium. Ruthenium red inhibits calcium transport through membrane channels.Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Fluoresceins: A family of spiro(isobenzofuran-1(3H),9'-(9H)xanthen)-3-one derivatives. These are used as dyes, as indicators for various metals, and as fluorescent labels in immunoassays.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Piperidines: A family of hexahydropyridines.Intracellular Fluid: The fluid inside CELLS.Glutathione: A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.Perfusion: Treatment process involving the injection of fluid into an organ or tissue.Sulfonamides: A group of compounds that contain the structure SO2NH2.Cation Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of positively charged molecules (cations) across a biological membrane.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Sulfobromophthalein: A phenolphthalein that is used as a diagnostic aid in hepatic function determination.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Tetrahydroisoquinolines: A group of ISOQUINOLINES in which the nitrogen containing ring is protonated. They derive from the non-enzymatic Pictet-Spengler condensation of CATECHOLAMINES with ALDEHYDES.Chloramphenicol Resistance: Nonsusceptibility of bacteria to the action of CHLORAMPHENICOL, a potent inhibitor of protein synthesis in the 50S ribosomal subunit where amino acids are added to nascent bacterial polypeptides.Plant Roots: The usually underground portions of a plant that serve as support, store food, and through which water and mineral nutrients enter the plant. (From American Heritage Dictionary, 1982; Concise Dictionary of Biology, 1990)5-Methoxytryptamine: Serotonin derivative proposed as potentiator for hypnotics and sedatives.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Nigericin: A polyether antibiotic which affects ion transport and ATPase activity in mitochondria. It is produced by Streptomyces hygroscopicus. (From Merck Index, 11th ed)Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates.Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.Thioridazine: A phenothiazine antipsychotic used in the management of PHYCOSES, including SCHIZOPHRENIA.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Buspirone: An anxiolytic agent and serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the BENZODIAZAPINES, but it has an efficacy comparable to DIAZEPAM.Stimulation, Chemical: The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.Indoleacetic Acids: Acetic acid derivatives of the heterocyclic compound indole. (Merck Index, 11th ed)Lysergic Acid Diethylamide: Semisynthetic derivative of ergot (Claviceps purpurea). It has complex effects on serotonergic systems including antagonism at some peripheral serotonin receptors, both agonist and antagonist actions at central nervous system serotonin receptors, and possibly effects on serotonin turnover. It is a potent hallucinogen, but the mechanisms of that effect are not well understood.Tetracyclines: Closely congeneric derivatives of the polycyclic naphthacenecarboxamide. (Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1117)Membrane Transport Modulators: Agents that affect ION PUMPS; ION CHANNELS; ABC TRANSPORTERS; and other MEMBRANE TRANSPORT PROTEINS.Ciprofloxacin: A broad-spectrum antimicrobial carboxyfluoroquinoline.Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism.Onium Compounds: Ions with the suffix -onium, indicating cations with coordination number 4 of the type RxA+ which are analogous to QUATERNARY AMMONIUM COMPOUNDS (H4N+). Ions include phosphonium R4P+, oxonium R3O+, sulfonium R3S+, chloronium R2Cl+Phosphates: Inorganic salts of phosphoric acid.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Dinitrophenols: Organic compounds that contain two nitro groups attached to a phenol.Potassium-Hydrogen Antiporters: Membrane proteins that allow the exchange of hydrogen ions for potassium ions across the cellular membrane. The action of these antiporters influences intracellular pH and potassium ion homeostasis.Uncoupling Agents: Chemical agents that uncouple oxidation from phosphorylation in the metabolic cycle so that ATP synthesis does not occur. Included here are those IONOPHORES that disrupt electron transfer by short-circuiting the proton gradient across mitochondrial membranes.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Erythromycin: A bacteriostatic antibiotic macrolide produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins.Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.Lanthanum: Lanthanum. The prototypical element in the rare earth family of metals. It has the atomic symbol La, atomic number 57, and atomic weight 138.91. Lanthanide ion is used in experimental biology as a calcium antagonist; lanthanum oxide improves the optical properties of glass.Drug Resistance, Multiple, Fungal: The ability of fungi to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance phenotype may be attributed to multiple gene mutations.Ion Exchange: Reversible chemical reaction between a solid, often one of the ION EXCHANGE RESINS, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Quinidine: An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Quipazine: A pharmacologic congener of serotonin that contracts smooth muscle and has actions similar to those of tricyclic antidepressants. It has been proposed as an oxytocic.Daunorubicin: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.
  • Increasing evidence supports the contention that many malignancies, including sporadic colorectal cancer, are driven by the self-renewing, chemotherapy-resistant cancer stem/stem-like cells (CSC/CSLC), underscoring the need for improved preventive and therapeutic strategies targeting CSCs/CSLCs. (aacrjournals.org)
  • Recent evidence suggests that epithelial cancers, including colorectal cancer are driven by a small sub-population of self-renewing, multi-potent cells termed cancer stem cells (CSCs) which are thought to be responsible for recurrence of cancer. (nih.gov)
  • Both cAMP and cGMP have been shown to have antiproliferative and proapoptotic effects in many cell types ( 15 , 16 ), and numerous studies have described the growth-inhibitory and apoptosis-inducing effects of various PDE inhibitors on certain tumor cell types, including colorectal cancer cells ( 17 - 20 ). (aacrjournals.org)
  • The investigation of platinum-based drug effect on tumor stem cells responsible for tumor generation and propagation is a novel and expanding field, and in the colorectal cancer casuistry they are many features uncovered. (iocn.ro)
  • Its inhibition by siRNA approach partially sensitized cells to various agents, thus linking for the first time the ALDH1A3 and chemoresistance in colorectal cancer. (biomedcentral.com)
  • These results indicate that the combination of APOA-I and AIBP has an obvious anticancer effect on colorectal cancer by promoting cholesterol efflux. (biomedcentral.com)
  • A new series of tetrahydroacridine derivatives with the fluorobenzoyl moiety was synthesized and evaluated for cytotoxic activity against lung cancer cell lines A549 and colorectal cancer HT29. (bvsalud.org)
  • In the present study, a high-throughput quantitative proteomics approach was applied to identify differentially expressed proteins of HCT116 colorectal cancer cell line with artesunate (ART) treatment. (mdpi.com)
  • Thus, by an examination of various cell lines exposed to different apoptotic stimuli, it has been demonstrated that the separate pharmacological blockade of volume-regulatory K + and Cl − channels prevents AVD and subsequent apoptosis. (physiology.org)
  • Furthermore, an interplay among AVD, ROS production, and TASK2 channels seems to be essential for permitting the cells to enter into apoptosis during STS exposure ( 22 ). (physiology.org)
  • Inhibition of PMCA4 using small interfering RNA did not induce cell death or augment sensitivity to the mitochondrial uncoupler carbonyl cyanide 3-chlorophenylhydrazone (CCCP) or tumor necrosis factor-related apoptosis-inducing ligand. (genes2cognition.org)
  • In addition, light-activated hypericin acts as a strong pro-oxidant agent with antineoplastic and antiangiogenic properties, since it effectively induces the apoptosis, necrosis or autophagy of cancer cells. (frontiersin.org)
  • ATP7A targeted small interfering RNA duplex at 100nM final concentration added into DDP-resistant cancer cells (EC109/DDP) markedly inhibited the expression of ATP7A as determined by Western blot (83.0%) and partially reversed DDP-resistance (37.09%), moreover, it also increased cell apoptosis at different DDP concentrations. (jcancer.org)
  • Mechanistic studies have shown that sulindac sulfone and several structurally related analogues can inhibit cyclic guanosine 3′,5′-monophosphate (cGMP) phosphodiesterase (PDE) activity at concentrations that are comparable with those required to inhibit colon tumor cell growth and induce apoptosis ( 12 - 14 ). (aacrjournals.org)
  • Effects of taspine on proliferation and apoptosis by regulating caspase-3 expression and the ratio of Bax/Bcl-2 in A431 cells. (rain-tree.com)
  • It is feasible to assess the platinum-treated stem cells, with accent on apoptosis, multidrug resistance, metabolism and cell signaling. (iocn.ro)
  • Chemotherapeutic drugs cause DNA damage and kill cancer cells mainly by apoptosis. (rupress.org)
  • To explore the pathway of p53-dependent cell death, we investigated if p53-dependent apoptosis after DNA damage is mediated by the CD95 (APO-1/Fas) receptor/ligand system. (rupress.org)
  • This rendered the cells sensitive to CD95-mediated apoptosis. (rupress.org)
  • 6 )) have shown that death induced in tumor cells by anticancer treatment is an active program of the cell which involves the CD95 system, one of the key regulatory systems of apoptosis. (rupress.org)
  • The presence of functional wild-type (wt) 1 p53 is closely coupled with efficient induction of CD95-mediated apoptosis in many (( 6 )-( 8 )) but not all (( 9 ), ( 10 )) cell types. (rupress.org)
  • The P-glycoprotein inhibitor PSC 833 causes apoptosis of cancer cells and induces a rise in the intracellular levels of ceramide. (cognizantcommunication.com)
  • Our aims were to determine whether a cause and effect relationship exists between these two actions of PSC 833, and to assess whether the PSC 833-induced apoptosis is restricted to transformed cells. (cognizantcommunication.com)
  • PSC 833 induced apoptosis in the human T leukemia cell lines: Molt-4 and Jurkat. (cognizantcommunication.com)
  • Analysis of the apoptosis in Molt-4 and Jurkat cells revealed that PSC 833 induced a rise in the cellular ceramide levels (as measured by the DG kinase assay). (cognizantcommunication.com)
  • On the other hand, PSC 833 did not induce apoptosis in normal peripheral blood T cells regardless of whether these cells were quiescent, activated, or proliferating. (cognizantcommunication.com)
  • Then, we examined the synergistic effect of AIBP and APOA-I on intestinal tumor growth and metastasis, as well as cell proliferation, viability, apoptosis, migration, and invasion and tumor-induced angiogenesis. (biomedcentral.com)
  • Cell viability and necrosi apoptosis was examined.Production level of singlet oxygen was detected with the photomultiplier-tube s/ -based singlet oxygen detection system. (pdtmed.org)
  • In PC-3 prostate cancer cells, Ispinesib (15 nM and 30 nM) blocks cell proliferation and induces apoptosis by regulating the expression levels of genes that controls apoptosis, cell proliferation, cell cycle, and cell signaling, such as EGFR, p27, p15, and IL-11. (selleckchem.com)
  • In BT-474 and MDA-MB-468 cells, Ispinesib (150 nM) induces apoptosis, as revealed by a higher proportion of apoptotic cells, lower antiapoptotic Bcl-X L level, and higher proapoptotic Bax and Bid levels. (selleckchem.com)
  • Using a small-molecule MDM2 antagonist, nutlin-3, to probe downstream p53 signaling we find that the cell-cycle arrest function of the p53 pathway is preserved in multiple tumor-derived cell lines expressing wild-type p53, but many have a reduced ability to undergo p53-dependent apoptosis. (pnas.org)
  • The p53 tumor suppressor plays a central role in protection from tumor development by inducing cell-cycle arrest or apoptosis in response to diverse stresses ( 1 ). (pnas.org)
  • AMTAC-06 significantly reduced the total viable Ehrlich tumor cells and increased sub-G1 peak, suggesting apoptosis was triggered. (bvsalud.org)
  • Subsequent assays showed that ART inhibits HCT116 cell proliferation through suppressing the fatty acid biosynthetic pathway and activating the mitochondrial apoptosis pathway. (mdpi.com)
  • doi:10.1016/j.canlet.2005.06.003 D. Peer, R. Margalit / Cancer Letters 237 (2006) 180-187 less-that allows the drug to diffuse across cell specificities, yet they function similarly in terms of membranes (influx and efflux). (pdfmedarticles.com)
  • Analyses included real-time quantitative PCR, immunoblotting and immunofluorescence analyses, radioactive tracer flux measurements, and biochemical analyses of cell viability and glutathione content. (biomedcentral.com)
  • This reflected neither altered expression of the oxaliplatin transporter Cu 2+ -transporter-1 (CTR1), nor changes in cellular reduced glutathione (GSH), although HCT116 cell resistance per se correlated with increased cellular GSH. (biomedcentral.com)
  • Disruptions to the redox balance occurred with both treatments in the two cell lines, characterised by shifts in the abundance of glutathione. (springer.com)
  • Although glutathione levels were elevated in human promyelocytic leukemia/TER286 cells, no changes in the expression of thiol-related genes including γ-glutamylcysteine synthetase, γ-glutamyl transpeptidase, or multidrug resistance protein were found. (aspetjournals.org)
  • The latent prodrug TER286 [γ-glutamyl-α-amino-β(2-ethyl- N , N , N ′, N ′-tetrakis(2-chloroethyl)phosphorodiamidate)-sulfonyl-propionyl-( R )-(−) phenylglycine] is the lead clinical candidate from a group of rationally designed glutathione (GSH) analogs that exploit high glutathione S- transferase P1-1 (GSTP1-1 or GSTπ) levels in solid tumors and drug-resistant cell populations ( Kauvar, 1996 ). (aspetjournals.org)
  • The saturable ECG uptake by the Caco-2 cells was sodium-independent but clearly dependent on a pH gradient. (aspetjournals.org)
  • The uptake of ECG in the Caco-2 cells increased 2-fold in the presence of 50 μM 3-[{3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl}-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK-571), suggesting the involvement of multidrug-associated protein (MRP)2 in efflux of ECG. (aspetjournals.org)
  • The main purpose of this study was to examine the Caco-2 cell uptake of ECG and EGCG, the tea flavonoids that have been shown to be the most biologically active, in comparison with EC and its geometric isomer (+)-catechin. (aspetjournals.org)
  • Mechanisms by which cancer cells acquire resistance to platinum agents include reduced cellular uptake, increased efflux, increased DNA repair and hypermethylation of MLH1 , part of the mismatch repair (MMR) system. (biomedcentral.com)
  • In HNO97 cells, a maximal uptake and internalization of up to 37.3% and 37.5%, respectively, was measured. (aacrjournals.org)
  • The current study aims at improving the pharmacokinetic profile of YM155 by its formulation in immunoliposomes that can achieve its enhanced delivery into tumor tissue and facilitate uptake in neuroblastoma cancer cells.PEGylated YM155 loaded liposomes composed of DPPC, cholesterol and DSPE-PEG 2000 were prepared via passive film-hydration and extrusion method. (chemweb.com)
  • The uptake level of PPa was significantly correlated with the decreased cell viability after PDT. (pdtmed.org)
  • ATP7A expressions in DDP-resistant cell sublines (EC109/DDP) were much higher than DDP-sensitive cell lines (EC109) at both mRNA and protein levels. (jcancer.org)
  • EGCG has been reported to inhibit mitogen activation protein kinases, the activation of activator protein-1, and cell transformation ( 6 - 8 ). (aacrjournals.org)
  • Total levels of farnesyl transferase protein subunits were similar in the parent and resistant cells, but, notably, the enzyme activity was markedly reduced in the resistant cell line compared with the parent cells. (aacrjournals.org)
  • In the present work we have characterized the permeability pathway induced by rotavirus infection after the beginning of viral protein synthesis and before the induction of cell lysis. (asm.org)
  • In particular, PCBP1 protein level increased 15.6 fold in HT-29/L-OHP cells compared to HT-29 cells. (oncotarget.com)
  • Factors setting the cerebral bioavailability of drugs include protein-unbound drug concentration in plasma, local cerebral blood flow, permeability across blood-brain interfaces, binding to neural cells, volume of cerebral fluid compartments, and cerebrospinal fluid secretion rate. (chemweb.com)
  • In SN38-resistant HCT116 and LoVo cells, SLC1A1 expression was down-regulated ~60 % and up-regulated ~4-fold, respectively, at both mRNA and protein level, whereas SLC1A3 protein was undetectable. (biomedcentral.com)
  • Bartosz, G. 2002-03-25 00:00:00 We employed human red blood cells as a model system to check the affinity of MRP1 (Multi-drug Resistance-associated Protein 1) towards fluorescein and a set of its carboxyl derivatives: 5/6-carboxyfluorescein (CF), 2′,7′-bis-(2-carboxyethyl)-5/6-carboxyfluorescein (BCECF) and calcein (CAL). (deepdyve.com)
  • Co-overexpression of AIBP and APOA-I more potently inhibited colon cancer cell-mediated tumor growth and metastasis compared to overexpression of each protein individually. (biomedcentral.com)
  • Genetic knockout of long myosin light chain kinase (MLCK) or treatment of wild-type mice with a highly specific peptide MLCK inhibitor prevented epithelial MLC phosphorylation, tight junction disruption, protein leak, and diarrhea following T cell activation. (100md.com)
  • TOP1 gene copy number and gene sequence, Top1 expression (mRNA and protein), Top1 enzymatic activity in the absence and presence of drug, and Top1-DNA cleavage complexes in drug treated cells. (biomedcentral.com)
  • NIH3T3 cells transfected with combinations of γ-GCS and multidrug resistance protein exhibited enhanced resistance to TER286, although the degree of resistance was impaired by cotransfection of GSTP1-1. (aspetjournals.org)
  • It can form a complex binding to target genes in a sequence-specific manner and is involved in the signal regulation of stem cells ( 20 , 21 ). (spandidos-publications.com)
  • The mutation in genes srtA and mucBP leads to a significant decrease in LMD-9 adhesion capacity to Caco-2 TC7 cells. (springer.com)
  • Recent evidence (( 3 )-( 6 )) suggests that genes that regulate apoptotic cell death may play an important role in determining the sensitivity of tumor cells to chemotherapy. (rupress.org)
  • Moreover, we observed that flavonoids pretreatment significantly induced the doxorubicin-mediated arrest at the phase of G2/M. Further, the combinations of doxorubicin with flavonoids significantly modulate the expression of drug response genes in KBCH R 8-5 cells. (beds.ac.uk)
  • The resistant cells showed cross-resistance to another, structurally different farnesyl transferase inhibitor-277, but not to GGTI-298. (aacrjournals.org)
  • A novel angiogenesis inhibitor impairs LoVo cell survival via targeting against human VEGFR and its signaling pathway of phosphorylation. (rain-tree.com)
  • Importantly, the non-selective glutamate transporter inhibitor DL-TBOA reduces chemotherapy-induced p53 induction and augments CRC cell death induced by SN38, while attenuating that induced by oxaliplatin. (biomedcentral.com)
  • Calpeptin, a calpain inhibitor, reversed the results of CaLa on FAK and pFAK cleavage in both cancers cell lines. (researchhunt.com)
  • In addition, we were using transcriptional reporter assays in E. coli and mammalian cells to decipher the possible mode of action. (wur.nl)
  • Cells were characterized by viability assays, flow cytometry, gene expression arrays and kinetic imaging. (biomedcentral.com)
  • Flow cytometry-based efflux assays were performed to examine KB-V1 cells incubated with either calcein AM (1 uM, red line) or calcein AM plus BEZ235, BI 2536, IKK 16, ispinesib, or bryostatin-1 (5 uM, blue line). (selleckchem.com)
  • 1 H nuclear magnetic resonance spectroscopy-based metabolic profiling was coupled with DNA damage-related assays (cell cycle, Comet assay, viability assays) to profile the comparative effects of watercress and PEITC in MCF-7 breast cancer cells and MCF-10A non-tumorigenic breast cells with and without exposure to IR. (springer.com)
  • The maximum E. coli cell-wall stress activity was measured at a concentration close to the onset of the mammalian cytotoxicity, while other adverse outcome pathways, such as the activation of aryl hydrocarbon and estrogenic receptor, the p53 tumour suppressor and the oxidative stress-related Nrf2 transcription factor, were induced at elevated concentrations compared to the response of mammalian cells. (wur.nl)
  • Previous studies have shown Chk1/2 inhibitors, such as UCN-01, can potentiate camptothecin-mediated cytotoxicity in p53 mutant cells by eliminating the DNA replication checkpoint. (aacrjournals.org)
  • however, when the nitric oxide levels are improved in resistant cells by providers additional than doxorubicin, the drug efflux is definitely reduced and the cytotoxicity is definitely refurbished . (ovarian-cancersymptoms.com)
  • This study aimed to further explore the mechanisms behind the ability of certain linear polyamidoamines (PAAs) to transfect cells with minimal cytotoxicity.The transfection efficiency of DNA complexed with a PAA of a molecular weight over 10 kDa or 25 kDa branched polyethyleneimine (BPEI) was compared in A549 cells using a luciferase reporter gene assay. (chemweb.com)
  • Raltitrexed and GW1843U89 showed potent cytotoxic activity and all four cell lines displayed similar cytotoxicity to these folate thymidylate synthase inhibitors. (cognizantcommunication.com)
  • Selected compounds showed similar cytotoxicity to the EAhy926 cell line (IC50 about 50 µM). (bvsalud.org)
  • The MDR reversal potential of these selected flavonoids against P-gp mediated drug resistance was analyzed by cytotoxicity assay in KBCH R 8-5 and MCF7/ADR cell lines. (beds.ac.uk)
  • Restitution of inducible wt p53 function restored the ability of p53 −/− Hep3B cells to upregulate the CD95 receptor in response to anticancer drugs. (rupress.org)
  • In this study, a group of Candida standard and clinical strains including C. albicans as well as several NAC species were employed to evaluate the antifungal potentials of palmatine (PAL) alone and in combination with fluconazole (FLC)/itraconazole (ITR) by microdilution method, checkerboard assay, gram staining, spot assay, and rhodamine 6G efflux test. (frontiersin.org)
  • The cytotoxicities of DDP in different cell lines were determined using the MTT assay. (jcancer.org)
  • reported that EGCG inhibited the phosphorylation of EGFR in A431 cells, and the result of a ligand-binding assay suggests that EGCG may block the binding of EGF to EGFR ( 21 ). (aacrjournals.org)
  • Chemoresistance and Akt activation in HT-29 and HT-29/L-OHP cells were analyzed by MTT assay and Western blot analysis. (oncotarget.com)
  • Using the cell-free Microarray Assay for Real-time Coregulator-Nuclear receptor Interaction (MARCoNI) it was demonstrated that, unlike the known PPAR-γ agonist rosiglitazone, neither the flavonoid aglycones nor the conjugates are agonistic ligands of the PPAR-γ receptor. (wur.nl)
  • Different concentrations were prepared and examined on SW-48 and HT-29 cell lines using 2-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay. (rjpharmacognosy.ir)
  • The cells were exposed to ECG ± various transport inhibitors and incubated at 37°C. Absorbed flavonoids were extracted and quantified by high-performance liquid chromatography. (aspetjournals.org)
  • Excess zinc is also toxic to cells. (hindawi.com)
  • This tissue represents a model system for studying ion absorption across polarised epithelial cells as it provides a major pathway for fish to acquire zinc directly from water whilst sharing a conserved zinc transporting system with mammals. (biomedcentral.com)
  • Appelt-Menzel A, Cubukova A, G nther K, Edenhofer F, Piontek J , Krause G, St ber T, Walles H, Neuhaus W, Metzger M (2017) Establishment of a human blood-brain barrier co-culture model mimicking the neurovascular unit using induced pluri- and multipotent stem cells. (charite.de)
  • B cker R , Krug SM , Fromm A , Nielsen HL, Fromm M , Nielsen H, Schulzke JD (2017) Campylobacter fetus impairs barrier function in HT-29/B6 cells through focal tight junction alterations and leaks. (charite.de)
  • HT29-dx cells CRT was destined to Pgp and only by silencing the second option the CRT-operated phagocytosis was refurbished, suggesting that Pgp impairs the practical activity of CRT and the tumour cells phagocytosis. (ovarian-cancersymptoms.com)
  • Our work suggests that the levels of nitric oxide and Pgp vitally modulate the acknowledgement of the tumour cells by dendritic cells, and proposes a fresh potential restorative approach against chemo-immunoresistant tumours. (ovarian-cancersymptoms.com)
  • It offers been found out that the anthracyclines immunogenicity relies on their ability to induce the tumour cells phagocytosis by immature dendritic cells (iDCs). (ovarian-cancersymptoms.com)
  • Therefore, downregulation of Wnt/GSK 3β/β-catenin pathway possibly will reduce the P-gp expression and induce chemosensitization in drug-resistant cells. (beds.ac.uk)
  • The hypothesis tested in the present study was that LXRa overexpression influence cancer growth modulating lipid metabolism in cancer cells. (omicsdi.org)
  • Omega 3 PUFAs were incorporated in whole lipids as well as in DRMs of MDR cells, and altered the lipid composition of these compartments. (biomedcentral.com)
  • After heptamerization, domains 1 and 2 form a flat ring, in which all carbohydrate-binding sites remain bound to cell surface carbohydrate chains, stabilizing the transmembrane beta-barrel in a position perpendicular to the plane of the lipid bilayer. (embl-heidelberg.de)
  • We 174254-13-8 have recently shown that doxorubicin mediates the exposure of CRT and the phagocytosis by iDCs thanks to the induction of iNOS in drug-sensitive cells: indeed neither the translocation of CRT nor the phagocytosis occurred in the doxorubicin-sensitive cells silenced for gene. (ovarian-cancersymptoms.com)
  • Doxorubicin was devoid of pro-immunogenic effects also in drug-resistant cells, where the anthracycline was not able to accumulate at a adequate degree to increase the synthesis of nitric oxide . (ovarian-cancersymptoms.com)
  • These results suggested that chemo- and immunoresistance to doxorubicin are purely connected, and may both depend on the lack of nitric oxide synthesis in drug-resistant cells. (ovarian-cancersymptoms.com)
  • We therefore focused on the molecular basis of this strong association between chemo- and immunoresistance, and we analysed whether the improved manifestation of Pgp in drug-resistant cells may impact the CRT-mediated phagocytosis, therefore contributing to their immunoresistant phenotype. (ovarian-cancersymptoms.com)
  • In a drug-sensitive origins of each mode shed light on the phenomena, tumor cell the drug can, thus, accumulate to a but complete molecular understanding is still into sufficient level that culminates in cell death the future. (pdfmedarticles.com)
  • The roles of cancer stem cells in cancer Under a recently-introduced nomenclature ABCB1 recurrence and in drug resistance-intrinsic and replaces p-glycoprotein, MRP1 is named ABCC1 with acquired-needs further studies. (pdfmedarticles.com)
  • The clue of the treatment resides in the proportion of stem cells inhibited by the drug in the whole tumoral population, and the project proposes to identify and characterize the changes which occur in colon carcinoma stem cells during platinum chemotherapy. (iocn.ro)
  • It can be used to study drug transport into the epithelial cells and across the intestine, by using sensitive detection techniques like use of radiolabelled compounds. (rroij.com)
  • Cancer cells are extremely heterogeneous, even in each individual patient, in terms of their malignant potential, drug sensitivity, and their potential to metastasize and cause relapse. (pnas.org)
  • Tumor cells at tumor/brain-interface often exist behind a functionally intact blood-brain barrier (BBB), and so are shielded from exposure to therapeutic drug concentrations. (bvsalud.org)
  • One resistant cell line harbored a pair of yet unreported TOP1 mutations (R364K and G717R) in close proximity to the drug binding site. (biomedcentral.com)
  • Flavonoids on P-gp expression and the components of Wnt signaling in drug-resistant KBCH R 8-5 cells were analyzed by western blotting and qRT-PCR. (beds.ac.uk)
  • All the flavonoids selected in this study significantly decreased the expression of Wnt and GSK 3β in KBCH R 8-5 cells and subsequently modulates P-gp overexpression in this drug-resistant cell line. (beds.ac.uk)
  • The present findings illustrate that the studied flavonoids significantly enhances doxorubicin-mediated cell death through modulating P-gp expression pattern by targeting Wnt/β-catenin signaling in drug-resistant KBCH R 8-5 cells. (beds.ac.uk)
  • Tumor-associated macrophages (TAMs) as one of the most abundant tumor-infiltrating stromal cell types have been shown to promote metastasis, drug resistance, and associated with a poor prognosis in CRC patients. (biomedcentral.com)
  • A 7-fold increase in catalase expression in the resistant cell line indicated an adaptive response to oxidative and electrophilic stress, and this was also reflected in the lower prevalence of drug-induced DNA single-strand breaks in the resistant cells. (aspetjournals.org)
  • Thus, selective targeting of susceptible tumor phenotypes is a strategy that should result in the "release" of more active drug in malignant cells compared with normal tissue, thereby achieving an improved therapeutic index. (aspetjournals.org)
  • In the present work we 1st looked into the molecular mechanisms by which high levels of nitric oxide induce the translocation of CRT to the cell surface, comparing the doxorubicin-sensitive human being colon malignancy HT29 cells and the doxorubicin-resistant HT29-dx cells. (ovarian-cancersymptoms.com)
  • HT-29 cells were exposed to gradually increased concentration of L-OHP to select L-OHP resistant HT-29/L-OHP cell line. (oncotarget.com)
  • Hypermalignant cancer cells, termed cancer stem cells or stemness-high cancer cells, have been isolated from patients with a variety of tumor types and found to be highly malignant, tumorigenic, and resistant to chemotherapies. (pnas.org)
  • SN-38 resistant cells with wild-type TOP1 remained sensitive to NSC 743400, while cells with mutant TOP1 was fully cross-resistant to both indenoisoquinolines. (biomedcentral.com)
  • A human promyelocytic leukemia /TER286-resistant cell line was selected by chronic, long-term exposure to the prodrug. (aspetjournals.org)
  • These results are consistent with responses in the TER286-resistant cells indicative of GSTP1-1-mediated mechanism of activation. (aspetjournals.org)
  • However, the specific PDE isozyme(s) responsible for its tumor cell growth-inhibitory activity has not been identified, nor has this effect been well studied with regard to the chemopreventive efficacy of conventional NSAIDs. (aacrjournals.org)
  • Although, achieving durable brain exposures of ispinesib is critical for adequate tumor cell engagement during mitosis, when tumor cells are vulnerable, for efficacy. (bvsalud.org)
  • In future studies of EGCG and other polyphenolic compounds in cell culture, SOD may be added to stabilize EGCG and to avoid possible artifacts. (aacrjournals.org)
  • Like other platinum-based anti-cancer compounds, L-OHP forms both inter- and intra-strand cross links in DNA as platinum (Pt)-DNA adducts, which prevent DNA replication and transcription, and cause cancer cell death. (oncotarget.com)
  • Studies concerning the action of platinum compounds against immune mechanisms focusing activated lymphocytes involved could bring novelties in the field of cancer cell biochemistry and function. (iocn.ro)
  • The project intends to investigate the percent of stem cells having genetic mutations, and the effect of platinum-based compounds on cell populations which display chemoresistance versus targeted anti-EGFR therapy. (iocn.ro)
  • 3. One of our objectives is to scan the lymphocyte populations implicated in antitumoral immune response, emphasizing the CD8 positive T lymphocytes and the natural killer cells, in order to establish the magnitude of the changes in human body immune response potential following the platinum compounds action. (iocn.ro)
  • Fluorescein is transported mainly in a passive way, while active efflux systems at least partially contribute to the transport of the other compounds. (deepdyve.com)
  • The cytotoxic activity of the compounds was compared on the somatic cell line-EAhy926. (bvsalud.org)
  • Compounds showed high cytotoxic activity on A549 cells (IC50 183.26-68.07 µM) and HT29 cells (IC50 68.41-19.70 µM), higher than controls-etoposide (IC50 451.47 µM) toward A549 and 5-fluorouracil (IC50 1626.85 µM) against HT29. (bvsalud.org)
  • Aminothiophene and aminothiazole compounds, and compositions comprising these compounds, described herein that inhibit efflux of chloride through a calcium-activated chloride channel are useful for treating diseases, disorders, and sequelae of diseases, disorders, and conditions that are associated with aberrantly increased chloride and fluid secretion, for example, secretory diarrhea. (patentsencyclopedia.com)
  • Radiation-induced damage activates several signal transduction pathways whose primary role is to detect genomic injury leading to cell cycle arrest and DNA repair. (springer.com)
  • DCUN1D3 activates SCFSKP2 ubiquitin E3 ligase activity and cell cycle progression under UV damage. (pianolarge.ml)
  • Cancer cell CAi activity, measured as cytoplasmic CO2 hydration rate (kf), ranged from high in colorectal HCT116 (∼2 s(-1)), bladder RT112 and colorectal HT29, moderate in fibrosarcoma HT1080 to negligible (i.e. spontaneous kf = 0.18 s(-1)) in cervical HeLa and breast MDA-MB-468 cells. (ox.ac.uk)
  • DL-TBOA co-treatment concentration-dependently augmented loss of cell viability induced by SN38, while strongly counteracting that induced by oxaliplatin, in both HCT116 and LoVo cells. (biomedcentral.com)
  • Histologically, esophageal cancer can be classified as adenocarcinoma and esophageal squamous cell carcinoma (ESCC) which is the most common histology in Asia ( 4 ). (jcancer.org)
  • Targeted therapies are regarded as promising approaches to increase 5-year survival rate of head and neck squamous cell carcinoma (HNSCC) patients. (aacrjournals.org)
  • Head and neck squamous cell carcinoma (HNSCC) represent more than 90% of all head and neck cancers and account for more than 5% of all malignant tumors worldwide ( 1 ). (aacrjournals.org)
  • We observed similar effects of EGCG in esophageal squamous cell carcinoma KYSE 150 cells and epidermoid squamous cell carcinoma A431 cells. (aacrjournals.org)
  • Although derived from a colon carcinoma, when cultured under specific conditions the cells become differentiated and polarized such that their phenotype, morphologically and functionally, resembles the enterocytes lining the small intestine. (cacoready.com)
  • In all cases, the development of colorectal carcinoma has been associated with the occurrence of sequential mutations in the cells of the intestinal epithelium (3). (scielo.br)
  • Materials and methods Materials Foetal bovine serum (FBS), penicillin-streptomycin (PS) and Roswell Park Funeral Company (RPMI) 1640 were supplied by Sigma Chemical Co. (St. Louis, MO, USA), plasticware for cell tradition was from Falcon (BD Biosciences, Bedford, MA, USA). (ovarian-cancersymptoms.com)
  • MDR1 gene encodes for P glycoprotein (P-gp), which plays an important role in the bioavailability and cell-toxicity limitation of a wide range of drugs and xenobiotics ( 15 ). (jcancer.org)