The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.
The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
A cell line derived from cultured tumor cells.
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Substances that are toxic to cells; they may be involved in immunity or may be contained in venoms. These are distinguished from CYTOSTATIC AGENTS in degree of effect. Some of them are used as CYTOTOXIC ANTIBIOTICS. The mechanism of action of many of these are as ALKYLATING AGENTS or MITOSIS MODULATORS.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Established cell cultures that have the potential to propagate indefinitely.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
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.
The action of a drug in promoting or enhancing the effectiveness of another drug.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
A 46-kD stimulatory receptor found on resting and activated NATURAL KILLER CELLS. It has specificity for VIRAL HEMAGGLUTININS that are expressed on infected cells.
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.
The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A calcium-dependent pore-forming protein synthesized in cytolytic LYMPHOCYTES and sequestered in secretory granules. Upon immunological reaction between a cytolytic lymphocyte and a target cell, perforin is released at the plasma membrane and polymerizes into transmembrane tubules (forming pores) which lead to death of a target cell.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Antibodies produced by a single clone of cells.
A 30 kDa stimulatory receptor found on resting and activated NATURAL KILLER CELLS.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A 44-kD stimulatory receptor found on activated NATURAL KILLER CELLS. It has specificity for VIRAL HEMAGGLUTININS that are expressed on infected cells.
Quaternary salts derived from tetrazoles. They are used in tests to distinguish between reducing sugars and simple aldehydes, for detection of dehydrogenase in tissues, cells, and bacteria, for determination of corticosteroids, and in color photography. (From Mall's Dictionary of Chemistry, 5th ed, p455)
Proteins secreted from an organism which form membrane-spanning pores in target cells to destroy them. This is in contrast to PORINS and MEMBRANE TRANSPORT PROTEINS that function within the synthesizing organism and COMPLEMENT immune proteins. These pore forming cytotoxic proteins are a form of primitive cellular defense which are also found in human LYMPHOCYTES.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
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.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
Cytolytic lymphocytes with the unique capacity of killing natural killer (NK)-resistant fresh tumor cells. They are INTERLEUKIN-2-activated NK cells that have no MAJOR HISTOCOMPATIBILITY COMPLEX restriction or need for antigen stimulation. LAK cells are used for ADOPTIVE IMMUNOTHERAPY in cancer patients.
Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
Unstable isotopes of chromium that decay or disintegrate emitting radiation. Cr atoms with atomic weights of 46-49, 51, 55, and 56 are radioactive chromium isotopes.
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.
A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
Semisynthetic conjugates of various toxic molecules, including RADIOACTIVE ISOTOPES and bacterial or plant toxins, with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; and ANTIGENS. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A protein phytotoxin from the seeds of Ricinus communis, the castor oil plant. It agglutinates cells, is proteolytic, and causes lethal inflammation and hemorrhage if taken internally.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
A synthetic amino acid that depletes glutathione by irreversibly inhibiting gamma-glutamylcysteine synthetase. Inhibition of this enzyme is a critical step in glutathione biosynthesis. It has been shown to inhibit the proliferative response in human T-lymphocytes and inhibit macrophage activation. (J Biol Chem 1995;270(33):1945-7)
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Elements of limited time intervals, contributing to particular results or situations.
A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.
Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).
An array of tests used to determine the toxicity of a substance to living systems. These include tests on clinical drugs, foods, and environmental pollutants.
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.)
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.
Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
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.
Glycoproteins found on the membrane or surface of cells.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
Toxic substances formed in or elaborated by bacteria; they are usually proteins with high molecular weight and antigenicity; some are used as antibiotics and some to skin test for the presence of or susceptibility to certain diseases.
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.
An encapsulated lymphatic organ through which venous blood filters.
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
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.
Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
Relating to the size of solids.
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.
A diazo-naphthalene sulfonate that is widely used as a stain.
Receptors that are specifically found on the surface of NATURAL KILLER CELLS. They play an important role in regulating the cellular component of INNATE IMMUNITY.
A cytologic technique for measuring the functional capacity of tumor stem cells by assaying their activity. It is used primarily for the in vitro testing of antineoplastic agents.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
An activating NK cell lectin-like receptor subfamily that regulates immune responses to INFECTION and NEOPLASMS. Members of this subfamily generally occur as homodimers.
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.
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.
Proteins prepared by recombinant DNA technology.
Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.
Tumors or cancer of the COLON.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The 140 kDa isoform of NCAM (neural cell adhesion molecule) containing a transmembrane domain and short cytoplasmic tail. It is expressed by all lymphocytes mediating non-MHC restricted cytotoxicity and is present on some neural tissues and tumors.
An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.
An oral anticoagulant that interferes with the metabolism of vitamin K. It is also used in biochemical experiments as an inhibitor of reductases.
Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors.
Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.
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.
A human liver tumor cell line used to study a variety of liver-specific metabolic functions.
Strongly cationic polymer that binds to certain proteins; used as a marker in immunology, to precipitate and purify enzymes and lipids. Synonyms: aziridine polymer; Epamine; Epomine; ethylenimine polymer; Montrek; PEI; Polymin(e).
A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
An experimental lymphocytic leukemia of mice.
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.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
Experimentally induced neoplasms of CONNECTIVE TISSUE in animals to provide a model for studying human SARCOMA.
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).
A vital dye used as an indicator and biological stain. Various adverse effects have been observed in biological systems.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.
An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
The rate dynamics in chemical or physical systems.
A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed)
Antimetabolites that are useful in cancer chemotherapy.
Immunoglobulins induced by antigens specific for tumors other than the normally occurring HISTOCOMPATIBILITY ANTIGENS.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
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.
Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.
This line KB is now known to be a subline of the ubiquitous KERATIN-forming tumor cell line HeLa. It was originally thought to be derived from an epidermal carcinoma of the mouth, but was subsequently found, based on isoenzyme analysis, HeLa marker chromosomes, and DNA fingerprinting, to have been established via contamination by HELA CELLS. The cells are positive for keratin by immunoperoxidase staining. KB cells have been reported to contain human papillomavirus18 (HPV-18) sequences.
Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
An aminoacridine derivative that intercalates into DNA and is used as an antineoplastic agent.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)
Naphthalene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
A subclass of natural killer cell receptors that perform an important role in the recognition of tumor cells by NK CELLS.
A unifocal malignant tumor that consists of atypical pathological MAST CELLS without systemic involvement. It causes local destructive growth in organs other than in skin or bone marrow.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)
The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.
Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Compounds that inhibit the activity of DNA TOPOISOMERASE I.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
Ribosome inactivating proteins consisting of only the toxic A subunit, which is a polypeptide of around 30 kDa.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)
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.
Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate.
Nanoparticles produced from metals whose uses include biosensors, optics, and catalysts. In biomedical applications the particles frequently involve the noble metals, especially gold and silver.
A nitroimidazole that sensitizes normally radio-resistant hypoxic cells to radiation. It may also be directly cytotoxic to hypoxic cells and has been proposed as an antineoplastic.
Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS.
Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
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.
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.
Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.
The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population.
Simultaneous resistance to several structurally and functionally distinct drugs.
Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.
A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.
Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
DNA present in neoplastic tissue.
The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.
Tumors or cancer of the LUNG.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.
A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens.
Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.
Enzymes that transfer the ADP-RIBOSE group of NAD or NADP to proteins or other small molecules. Transfer of ADP-ribose to water (i.e., hydrolysis) is catalyzed by the NADASES. The mono(ADP-ribose)transferases transfer a single ADP-ribose. POLY(ADP-RIBOSE) POLYMERASES transfer multiple units of ADP-ribose to protein targets, building POLY ADENOSINE DIPHOSPHATE RIBOSE in linear or branched chains.
Toxins produced, especially by bacterial or fungal cells, and released into the culture medium or environment.
Saturated azacyclopropane compounds. They include compounds with substitutions on CARBON or NITROGEN atoms.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Tumors or cancer of the human BREAST.
A general term for various neoplastic diseases of the lymphoid tissue.
Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.
Nanometer-sized, hollow, spherically-shaped objects that can be utilized to encapsulate small amounts of pharmaceuticals, enzymes, or other catalysts (Glossary of Biotechnology and Nanobiotechnology, 4th ed).
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
The process by which chemical compounds provide protection to cells against harmful agents.
Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).
A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)
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.
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.
Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides.
An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.
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).
Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)
A cinnamate derivative of the shikamate pathway found in CLOVE OIL and other PLANTS.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS.
Stable chromium atoms that have the same atomic number as the element chromium, but differ in atomic weight. Cr-50, 53, and 54 are stable chromium isotopes.
Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.
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.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail" formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.

Crystal structure of an MHC class I presented glycopeptide that generates carbohydrate-specific CTL. (1/8548)

T cell receptor (TCR) recognition of nonpeptidic and modified peptide antigens has been recently uncovered but is still poorly understood. Immunization with an H-2Kb-restricted glycopeptide RGY8-6H-Gal2 generates a population of cytotoxic T cells that express both alpha/beta TCR, specific for glycopeptide, and gamma/delta TCR, specific for the disaccharide, even on glycolipids. The crystal structure of Kb/RGY8-6H-Gal2 now demonstrates that the peptide and H-2Kb structures are unaffected by the peptide glycosylation, but the central region of the putative TCR binding site is dominated by the extensive exposure of the tethered carbohydrate. These features of the Kb/RGY8-6H-Gal2 structure are consistent with the individual ligand binding preferences identified for the alpha/beta and gamma/delta TCRs and thus explain the generation of a carbohydrate-specific T cell response.  (+info)

Crystal structures of two H-2Db/glycopeptide complexes suggest a molecular basis for CTL cross-reactivity. (2/8548)

Two synthetic O-GlcNAc-bearing peptides that elicit H-2Db-restricted glycopeptide-specific cytotoxic T cells (CTL) have been shown to display nonreciprocal patterns of cross-reactivity. Here, we present the crystal structures of the H-2Db glycopeptide complexes to 2.85 A resolution or better. In both cases, the glycan is solvent exposed and available for direct recognition by the T cell receptor (TCR). We have modeled the complex formed between the MHC-glycopeptide complexes and their respective TCRs, showing that a single saccharide residue can be accommodated in the standard TCR-MHC geometry. The models also reveal a possible molecular basis for the observed cross-reactivity patterns of the CTL clones, which appear to be influenced by the length of the CDR3 loop and the nature of the immunizing ligand.  (+info)

Control of metastasis by Asn-linked, beta1-6 branched oligosaccharides in mouse mammary cancer cells. (3/8548)

Studies in cell lines and malignant human tissues have shown that increased cell-surface Asn-linked beta1-6(GlcNAcbeta1-6Man) branching is associated with increased tumorigenic and metastatic properties. In this study, three mouse mammary cancer cell lines were transfected with an expression vector containing the mouse cDNA for N-acetylglucosaminyltransferase V (GlcNAcT-V EC 2.4.1.155), the glycosyltransferase responsible for initiating beta1-6 branching on Asn-linked carbohydrates. The cell lines were screened for increased cytotoxicity to L-PHA, a lectin specific for beta1-6 branching structures. Cell lines exhibiting increased L-PHA cytotoxicity expressed increased levels of beta1-6 branching structures. Northern blots detected the presence of GlcNAcT-V transcribed from the expression vector in the L-PHA sensitive cell lines. After injection into the tail veins of mice, transfected cell lines with increased beta1-6 branching on the cell surface formed elevated levels of lung tumors relative to control transfected cell lines (P < 0.002). Western blots of membrane proteins from GlcNAcT-V transfected and control cells probed with the lectins DSA and WGA did not show an increase in polyN-acetyllactosamine and sialic acid content in the transfected cell lines. These results demonstrate that a specific increase in beta1-6 branching due to an elevation in GlcNAcT-V expression increases metastatic potential.  (+info)

Giardia induces proliferation and interferon gamma production by intestinal lymphocytes. (4/8548)

BACKGROUND: Murine intraepithelial lymphocytes kill Giardia lambia; responses of human intestinal lymphocytes to this parasite are unknown. AIMS: To examine giardia induced proliferation, interferon gamma production, migration, and cytotoxicity by lymphocytes from the human intestine and peripheral blood. METHODS: Giardia were added to intraepithelial lymphocytes, lamina propria lymphocytes, and peripheral blood lymphocytes, obtained from jejunal mucosa and blood of otherwise healthy patients undergoing gastric bypass surgery for morbid obesity. Proliferation was measured by 3H-thymidine incorporation; frequency of proliferation precursors, by limiting dilution analysis; interferon gamma production, by ELISA; cytotoxicity, by 51Cr release of radiolabelled giardia and by release of serine esterases by effector lymphocytes that mediate cytotoxicity. RESULTS: The CD4+ T lymphocytes from intestine and blood proliferated in response to giardia. The stimulus by the parasite was mitogenic rather than antigenic due to the fact that the peak response was on day 3 rather than day 6, and the large number of precursors was in the range of that for mitogens. CD4+ T lymphocytes from both sites produced interferon gamma in response to giardia. Lymphocytes did not migrate towards or kill the parasite. CONCLUSIONS: Giardia induced the same degree of proliferation and interferon gamma production by CD4+ T lymphocytes in intestine and blood, but did not trigger cytotoxicity or migration.  (+info)

Enhanced tumor growth and invasiveness in vivo by a carboxyl-terminal fragment of alpha1-proteinase inhibitor generated by matrix metalloproteinases: a possible modulatory role in natural killer cytotoxicity. (5/8548)

Matrix metalloproteinases (MMPs) are believed to contribute to the complex process of cancer progression. They also exhibit an alpha1-proteinase inhibitor (alphaPI)-degrading activity generating a carboxyl-terminal fragment of approximately 5 kd (alphaPI-C). This study reports that overexpression of alphaPI-C in S2-020, a cloned subline derived from the human pancreas adenocarcinoma cell line SUIT-2, potentiates the growth capability of the cells in nude mice. After stable transfection of a vector containing a chimeric cDNA encoding a signal peptide sequence of tissue inhibitor of metalloproteinase-1 followed by cDNA for alphaPI-C into S2-020 cells, three clones that stably secrete alphaPI-C were obtained. The ectopic expression of alphaPI-C did not alter in vitro cellular growth. However, subcutaneous injection of the alphaPI-C-secreting clones resulted in tumors that were 1.5 to 3-fold larger than those of control clones with an increased tendency to invasiveness and lymph node metastasis. These effects could be a result of modulation of natural killer (NK) cell-mediated control of tumor growth in nude mice, as the growth advantage of alphaPI-C-secreting clones was not observed in NK-depleted mice, and alphaPI-C-secreting clones showed decreased NK sensitivity in vitro. In addition, production of alphaPI and generation of the cleaved form of alphaPI by MMP were observed in various human tumor cell lines and in a highly metastatic subline of SUIT-2 in vitro. These results provide experimental evidence that the alphaPI-degrading activity of MMPs may play a role in tumor progression not only via the inactivation of alphaPI but also via the generation of alphaPI-C.  (+info)

Suppression of angiogenesis, tumorigenicity, and metastasis by human prostate cancer cells engineered to produce interferon-beta. (6/8548)

We determined whether the IFN-beta gene can be used to suppress angiogenesis, tumor growth, and metastasis of human prostate cancer cells growing in the prostate of nude mice. Highly metastatic PC-3M human prostate cancer cells were engineered to constitutively produce murine IFN-beta subsequent to infection with a retroviral vector containing murine IFN-beta cDNA. Parental (PC-3M-P), control vector-transduced (PC-3M-Neo), and IFN-beta-transduced (PC-3M-IFN-beta) cells were injected into the prostate (orthotopic) or subcutis (ectopic) of nude mice. PC-3M-P and PC-3M-Neo cells produced rapidly growing tumors and regional lymph node metastases, whereas PC-3M-IFN-beta cells did not. PC-3M-IFN-beta cells also suppressed the tumorigenicity of bystander nontransduced prostate cancer cells. PC-3M-IFN-beta cells produced small tumors (3-5 mm in diameter) in nude mice treated with anti-asialo GM1 antibodies and in severe combined immunodeficient/Beige mice. Immunohistochemical staining revealed that PC-3M-IFN-beta tumors were homogeneously infiltrated by macrophages, whereas control tumors contained fewer macrophages at their periphery. Most tumor cells in the control tumors were stained positive by an antibody to proliferative cell nuclear antigen; very few were positively stained by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In sharp contrast, PC-3M-IFN-beta tumors contained fewer proliferative cell nuclear antigen-positive cells and many terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling-positive cells. Staining with antibody against CD31 showed that control tumors contained more blood vessels than PC-3M-IFN-beta tumors. PC-3M-IFN-beta cells were more sensitive to lysis mediated by natural killer cells in vitro or to cytostasis mediated by macrophages than control transduced cells. Conditioned medium from PC-3M-IFN-beta cells augmented splenic cell-mediated cytolysis to control tumor cells, which could be neutralized by antibody against IFN-beta. Collectively, the data suggest that the suppression of tumorigenicity and metastasis of PC-3M-IFN-beta cells is due to inhibition of angiogenesis and activation of host effector cells.  (+info)

Rapid death of adoptively transferred T cells in acquired immunodeficiency syndrome. (7/8548)

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) probably play the major role in controlling HIV replication. However, the value of adoptive transfer of HIV-specific CTL expanded in vitro to HIV+ patients has been limited: this contrasts with the success of CTL therapy in treating or preventing Epstein-Barr virus and cytomegalovirus disease after bone marrow transplantation (BMT). We investigated the fate of expanded HIV-specific CTL clones in vivo following adoptive transfer to a patient with acquired immunodeficiency syndrome (AIDS). Two autologous CTL clones specific for HIV Gag and Pol were expanded to large numbers (>10(9)) in vitro and infused into an HIV-infected patient whose viral load was rising despite antiretroviral therapy. The fate of one clone was monitored by staining peripheral blood mononuclear cells (PBMCs) with T-cell receptor-specific tetrameric major histocompatibility complex (MHC)-peptide complexes. Although the CTL transfer was well tolerated, there were no significant changes in CD4 and CD8 lymphocyte counts and virus load. By tracking an infused clone using soluble MHC-peptide complexes, we show that cells bearing the Gag-specific T-cell receptors were rapidly eliminated within hours of infusion through apoptosis. Thus, the failure of adoptively transferred HIV-specific CTL to reduce virus load in AIDS may be due to rapid apoptosis of the infused cells, triggered by a number of potential mechanisms. Further trials of adoptive transfer of CTL should take into account the susceptibility of infused cells to in vivo apoptosis.  (+info)

Contribution of natural killer cells to inhibition of angiogenesis by interleukin-12. (8/8548)

Interleukin-12 (IL-12) inhibits angiogenesis in vivo by inducing interferon-gamma (IFN-gamma) and other downstream mediators. Here, we report that neutralization of natural killer (NK) cell function with antibodies to either asialo GM1 or NK 1.1 reversed IL-12 inhibition of basic fibroblast growth factor (bFGF)-induced angiogenesis in athymic mice. By immunohistochemistry, those sites where bFGF-induced neovascularization was inhibited by IL-12 displayed accumulation of NK cells and the presence of IP-10-positive cells. Based on expression of the cytolytic mediators perforin and granzyme B, the NK cells were locally activated. Experimental Burkitt lymphomas treated locally with IL-12 displayed tumor tissue necrosis, vascular damage, and NK-cell infiltration surrounding small vessels. After activation in vitro with IL-12, NK cells from nude mice became strongly cytotoxic for primary cultures of syngeneic aortic endothelial cells. Cytotoxicity was neutralized by antibodies to IFN-gamma. These results document that NK cells are required mediators of angiogenesis inhibition by IL-12, and provide evidence that NK-cell cytotoxicity of endothelial cells is a potential mechanism by which IL-12 can suppress neovascularization.  (+info)

Mechanisms of T cell-mediated cytotoxicity remain poorly defined at the molecular level. To investigate some of these mechanisms, we used as target cells, on the one hand, thymocytes from lpr and gld mouse mutants, and on the other hand, L1210 cells transfected or not with the apoptosis-inducing Fas molecule. These independent mutant or transfectant-based approaches both led to the conclusion that Fas was involved in the Ca(2+)-independent component of cytotoxicity mediated by at least two sources of T cells, namely nonantigen-specific in vitro activated hybridoma cells, and antigen-specific in vivo raised peritoneal exudate lymphocytes. Thus, in these cases, T cell-mediated cytotoxicity involved transduction via Fas of the target cell death signal. ...
To investigate the molecular mechanisms by which the PBAF complex regulates the sensitivity of B16F10 tumor cells to T cell-mediated killing, we examined the transcriptome of PBAF-deficient B16F10 cells by RNA-seq. Arid2- and Pbrm1-deficient B16F10 cells shared similar gene expression profiles (fig. S12, A and B), consistent with their critical role in the PBAF complex. The transcriptome of Brd7 mutant B16F10 cells was more distinct, suggesting that Brd7 may also have PBAF-independent functions (fig. S12A). mRNAs for a number of metabolic pathways were concordantly down-regulated in Arid2 and Pbrm1 mutant cells compared to control B16F10 tumor cells, in particular gene sets associated with mTORC1 activation and cholesterol homeostasis (fig. S12, C and D, and fig. S13). mTORC1 was also a major resistance pathway for T cell-mediated cytotoxicity in the CRISPR-Cas9 screen (Fig. 1D).. Silencing of BAF200 (Arid2) with a small interfering RNA was shown to reduce the expression of interferon induced ...
We have developed a non-radioactive flow-cytometry assay to monitor and quantify the target-cell killing activities mediated by cytotoxic T lymphocytes (CTLs). This flow-cytometry CTL (FCC) assay is predicated on measurement of CTL-induced caspase activation in target cells through detection of the …
Harris, J W., Response of primary and secondary cytotoxic t lymphocytes to hyperthermia. Abstr. (1977). Subject Strain Bibliography 1977. 2592 ...
B.L.S. conceived and directed the project; M.S., P.W.H., F.M.H., and S.G.D. characterized the participant cohort and procured clinical samples; B.E.K. conducted laboratory assays and data analysis; B.E.K. and B.L.S. prepared, wrote, and edited the manuscript; all authors read and approved the manuscript. ...
T cells are crucial mediators of tissue rejection and long-lived immune protection. While HLA class I-restricted CD8-positive T cells are the primary effectors of tissue destruction, CD4-positive T cells support their expansion and memory formation. The identification of T cell target antigens is a prerequisite for the rational development of specific tumor immunotherapies. T cells recognize peptides bound to and presented by HLA molecules on the surfaces of target cells. The peptides are processed from proteins derived from any subcellular compartment. In this way, T cells sense differences between tumor and normal cells. Their sensitivity is exceptional in several aspects: On the one hand, even changes at single amino acid positions can be detected by T cells; on the other hand, the presence of very few peptide-HLA-complexes on target cell surfaces is sufficient for effective T cell recognition. Since 1991 a variety of T cell-recognized tumor-associated antigens has been published. A current ...
In this study, the in vitro and in vivo antitumor properties of the IL-2-activated MNCs from UCBCs in comparison with IL-2-activated MNCs from PBCs were explored. The NK cytotoxicity levels of UCBCs were very low compared with PBCs prior to in vitro activation (data not shown). After IL-2 activation, however, there was significant antitumor cytotoxicity against NK-sensitive/LAK-resistant and LAK-sensitive tumor target cells (Fig. 1)⇓ . Similar results have been observed by other investigators (20, 21, 22, 23, 24, 25, 26) . The activated UCBCs were not only cytotoxic to hematological malignant cells but also considerably cytotoxic to human breast cancer cells (Fig. 2)⇓ . The level of cytotoxicity of activated cord blood cells against breast cancer was not different from that of similarly activated MNCs from peripheral blood apheresis product. This result is different from what we observed with K562 and Raji tumor targets. The precise reason for this difference is not clear at this ...
We have shown that a KIR-CAR can be simply constructed by swapping the two immunoglobulin-like domains of the KIR2DS2 ectodomain with an scFv capable of binding a desired target antigen. When delivered to T cells together with DAP12, this KIR-based CAR triggers antigen-specific cytotoxicity, cytokine production, and proliferation that is comparable with second-generation CD3ζ-based CARs in vitro without the need for additional domains from costimulatory receptors. The ability of a KIR-based CAR to activate T cells in the absence of added costimulation is interesting in light of the critical importance of costimulation for full T-cell activation and acquisition of effector function. KIR2DS2, the natural KIR upon which the presented KIR-CAR is based, has previously been reported to deliver a costimulation-like signal to T cells. In these studies, engagement of the KIR in T-cell clones lacking DAP12 expression augmented anti-CD3-induced IFNγ production (16). The mechanism of this costimulatory ...
Knowledge of the interactions between MHC-unrestricted cytotoxic effector cells and solid tumour cells is essential for introducing more effective NK cell-based immunotherapy protocols into clinical practise. Here, to begin to obtain an overview of the possible universe of molecules that could be in …
RefSeq Summary (NM_005931): This gene encodes a heavily glycosylated protein which is a ligand for the NKG2D type II receptor. Binding of the ligand activates the cytolytic response of natural killer (NK) cells, CD8 alphabeta T cells, and gammadelta T cells which express the receptor. This protein is stress-induced and is similar to MHC class I molecules; however, it does not associate with beta-2-microglobulin or bind peptides. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014 ...
RefSeq Summary (NM_005931): This gene encodes a heavily glycosylated protein which is a ligand for the NKG2D type II receptor. Binding of the ligand activates the cytolytic response of natural killer (NK) cells, CD8 alphabeta T cells, and gammadelta T cells which express the receptor. This protein is stress-induced and is similar to MHC class I molecules; however, it does not associate with beta-2-microglobulin or bind peptides. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014 ...
Anybody that has played the beautiful game at a junior level may have once heard this little chestnut from a well-meaning coach: if you dont shoot, you dont score. True enough, but it is actually good quality shots, e.g. a shot on target, that are the key to scoring.
Quickly and accurately calculate the cell cytotoxicity from absorbance data obtained in lab assays, improving overall lab performance.
Protein levels regressed against four cytotoxicity phenotypes using fixed effect or mixed effect models representing the three biological replicates.We analyzed
اطلاعات مندرج در این پایگاه فقط جهت مطالعه کاربران با رعایت شرایط اعلام شده است. نسخه‌برداری و بازنشر اطلاعات به هر روش، در هر نوع رسانه و با هر هدفی ممنوع و پیگرد قانونی دارد. ...
CTLPF - Cytotoxic T-Lymphocyte Precursor Frequency. Looking for abbreviations of CTLPF? It is Cytotoxic T-Lymphocyte Precursor Frequency. Cytotoxic T-Lymphocyte Precursor Frequency listed as CTLPF
TY - JOUR. T1 - Monocyte- and natural killer cell-mediated spontaneous cytotoxicity against human noncultured solid tumor cells. AU - Itoh, Kyogo. AU - Platsoucas, Chris D.. AU - Balch, Charles M.. PY - 1987. Y1 - 1987. N2 - Unstimulated human peripheral blood mononuclear cells from healthy donors exhibited spontaneous cytotoxicity against noncultured solid tumor targets in a 12- to 24-hr 51Cr release or 111In release assay. Both purified monocytes (, 99% monocytes) and natural killer (NK)-enriched lymphocytes exhibited comparable levels of spontaneous cytotoxicity against fresh melanoma tumor targets. This cytotoxicity was observed under endotoxin-free conditions. NK-depleted lymphocytes did not lyse the melanoma targets. Culture supernatants of monocytes incubated with the melanoma tumor cells did not exhibit cytotoxic activity against these targets. Purified monocytes lacked NK activity against the K562 targets in a 4-hr 51Cr release assay. Treatment of the monocytes with anti-Leu 11b and ...
Hence, the hypothesis that UL18 replaces class I MHC molecules to prevent NK cell lysis does not seem to apply to hCMV-infected HFFs and transfected epithelial and ovary cells (293, COS-7, and CHO-K1). It was recently reported that UL18 inhibits NK cell lysis of 721.221 B lymphoblastoid targets, mediated through CD94 ((11)). In repeated studies, we never observed inhibition of NK cell killing against UL18 expressing targets using clones with functional CD94 or KIR. In view of this discrepancy, several aspects of the previous report should be highlighted. First, in the prior study UL18 was transfected into 721.221 targets; however, transfectants were isolated on the basis of surface β2M expression, not UL18. Second, we have failed to generate stable UL18 transfectants in 721.221 or in 15 other human or mouse lines, because it seems that prolonged expression (,2 wk) of UL18 results in cell death. We could only generate UL18 transfectants in high efficiency transient transfection systems such as ...
Ulm C, Saffarzadeh M, Mahavadi P, Müller S, Prem G, Saboor F, Simon P, Middendorff R, Geyer H, Henneke I, Bayer N, Rinné S, Lütteke T, Böttcher-Friebertshäuser E, Gerardy-Schahn R, Schwarzer D, Mühlenhoff M, Preissner KT, Günther A, Geyer R, Galuska SP., Cell Mol Life Sci 70(19), 2013 ...
TY - JOUR. T1 - Rapid and long-term changes to host cytotoxic T lymphocyte precursors reactive to donor antigens caused by intravenous injection of histoincompatible lymphocytes. AU - Martin, Diego R.. AU - Sheng-Tanner, Xiaofang. AU - Miller, Richard G.. PY - 1992/7. Y1 - 1992/7. N2 - It has been shown previously that a single intravenous injection of mouse F, LNC into either parent results in a rapid reduction in the ability of the recipient to generate CTL reactive against donor antigens in an in vitro MLR. The underlying mechanism appears to be the in-activation of host CTL precursors that can recognize donor lymphocytes that have entered the recirculating pool. The donor lymphocytes may be acting as functionally deleting APC, or veto cells. Here, we have injected C57BL/6 (B6) mice with (C57BL/6XDBA/2) F, (FO LNC. The CTL response against donor LNC was maximally reduced by 2 days and stayed reduced for at least 6 weeks, but ultimately recovered to normal levels. The response reduction ...
TY - JOUR. T1 - Characterization of Cord Blood Natural Killer and Lymphokine Activated Killer Lymphocytes Following Ex Vivo Cellular Engineering. AU - Ayello, Janet. AU - van de Ven, Carmella. AU - Fortino, Weiwei. AU - Wade-Harris, Cheryl. AU - Satwani, Prakash. AU - Baxi, Laxmi. AU - Simpson, Lynn L.. AU - Sanger, Warren G. AU - Pickering, Diana. AU - Kurtzberg, Joanne. AU - Cairo, Mitchell S.. PY - 2006/6/1. Y1 - 2006/6/1. N2 - Cord blood (CB) natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic cells are poorly characterized but might be used to treat minimal residual and/or recurrent malignant disease. Currently, there is no mechanism to use CB for adoptive cancer cellular immunotherapy after CB transplantation (CBT). Recognizing this as a deficiency, we hypothesized that CB aliquots could be engineered ex vivo for potential donor lymphocyte infusion after CBT. Cryopreserved CB aliquots were thawed, depleted of monocytes, and cultured in serum-free medium alone or serum-free ...
A low affinity receptor for IgG immune complexes, Fc gamma RIII(CD16), is expressed on human NK cells as an integral membrane glycoprotein anchored through a tr
Several lines of data have suggested a possible link between the indoleamine 2,3-dioxygenase (IDO)-like protein IDO2 and cancer. First, IDO2 expression has been described in human tumors, including renal, gastric, colon, and pancreatic tumors. Second, the apparent selective inhibition of IDO2 by the D stereoisomer of the IDO blocker 1-methyl-tryptophan (1MT), which tends to be more active than the L-isomer in a variety of biological assays for IDO function, suggests that IDO2 may be important to sustain immune escape and growth of tumors. Especially, D-1MT heightens chemotherapeutic efficacy in mouse models of cancer in a nontoxic fashion. Here, we describe the immunogenicity of IDO2 by showing the presence of spontaneous cytotoxic T-cell reactivity against IDO2 in peripheral blood of both healthy donors and cancer patients. Furthermore, we show that these IDO2-specific T cells are cytotoxic effector cells that recognize and kill tumor cells. Our data suggest that IDO2 might be a useful target ...
Insufficient natural killer cell responses against retroviruses: how to improve NK cell killing of retrovirus-infected cells. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Evaluation of adjuvants at the mucosal area for the development of innovative mucosal vaccine against PRRS. Presented at USDA and NPB meeting - Invited Presentation, Des Moines, IA, US,USA. (June 2009). Alternative models for study of respiratory diseases: Pig is a useful animal model to address both infectious and non-infectious lung diseases. Presented at Immunologists Round Table meeting - Invited Presentation, Columbus, OH, US,USA. (November 2010). A non-radioactive colorimetric assay to detect Natural Killer cell-mediated cytotoxicity. Presented at Immunologists Round Table Meeting - Invited Presentation, Wooster, OH, US,USA. (February 2010). Development of novel mucosal vaccines for the control of PRRS outbreaks.. Presented at USDA NPB meeting - Invited Presentation, Des Moines, IA, US,USA. (June 2010). Mucosal vaccine to protect against porcine reproductive and respiratory syndrome: a new perspective. Presented at 9th International Veterinary Immunology Society (IVIS) meeting - ...
The ligation of CD28 by B7.1 delivers a well-characterized, and perhaps the most potent, antigen-independent costimulatory signal to T cells, resulting in an increase in the production of T-helper 1-associated cytokines important in promoting antitumor CTL responses. B7.1 can also increase expression of the IL-2 receptor on T cells, prevent activation-induced T-cell death, and trigger natural killer cell cytotoxicity (19, 20). Whereas conferring B7 expression on tumor cells can enhance antitumor responses, it is also apparent that provision of B7 expression is not sufficient to induce immunity against nonimmunogenic tumors (21). Combining B7 expression with immune-stimulatory cytokine expression has been shown to augment tumor immunity. Synergy between B7.1 costimulation and IL-12 has been shown in melanoma models as well as models of breast cancer, lymphoma, hepatocellular cancer, head and neck cancer, and multiple myeloma (15, 22-26). We examined the safety and toxicity of the intratumoral ...
The propensity of HIV-1 for genetic variation, a consequence of error-prone reverse transcription combined with high rates of replication, is thought to contribute to the establishment of persistent infection in the host despite the presence of a vigorous antiviral immune response. Protective immunity to viruses is mediated primarily by cytotoxic T lymphocytes, which recognize viral peptides of 8-11 amino acids bound to major histocompatibility complex class I molecules on the surface of infected cells. In this review we examine the mechanisms by which mutation within peptide antigen-encoding regions of the viral genome enables HIV-1 to evade recognition by virus-specific cytotoxic T lymphocytes. The discussion is relevant to other genetically unstable viruses and more generally to intracellular pathogens of variable antigenicity.
Dear all, Our lab would like to use flow cytometry for the measuring natural killer cell cytotoxicity. Does anyone have a working protocol that can share with us? Also, could we use 24 hrs. old human whole blood instead of PBMC for the assay? It will be really appreciated if you can provide us with valuable pointers. Thanks in advance. Lee Lam CDC Atlanta, Georgia Phone: 404-639-2725 Fax: 404-639-4838 E-mail: LXL7 at CDC.GOV ,mailto:LXL7 at CDC.GOV ...
TY - JOUR. T1 - Adhesion and activation molecules expressed by human natural killer cells. AU - Santoni, Angela. AU - Gismondi, Angela. AU - Paolini, Rossella. AU - Procopio, Antonio. AU - Morrone, Stefania. AU - Mainiero, Fabrizio. AU - Santoni, Giorgio. AU - Piccoli, Mario. AU - Frati, Luigi. PY - 1991/2. Y1 - 1991/2. N2 - Our study concerns the expression and the regulation of adhesion and activation receptors on human NK cells. In particular we provide evidence on: a) the expression on fresh human NK cells of VLA-4, VLA-5 and VLA-6, extracellular matrix (ECM) receptors of integrin family capable of mediating their adhesion to FN and LM; b) the role of PKC on the regulation of CD16, a differentiation antigen associated with FcγR type III expressed by all NK cells, which mediate ADCC activity and trigger lymphokine production.. AB - Our study concerns the expression and the regulation of adhesion and activation receptors on human NK cells. In particular we provide evidence on: a) the ...
This sensitivity allows natural killer cells to vigorously initiate natural killer cytotoxicity (by emptying granules of porforin and granzyme) and inflammation as soon as pathogenesis is detected, and is essential to protection against viruses and tumors. Natural killer cells have genomic (not needed recombination, or RAG-independent) cell surface receptors which recognize classical Class I MHC molecules (and structural relatives like MICA, RAE-1 and H-60).. Natural killer cells lack TcRs, CD4s and CD8; instead, they have: cell-surface activating receptors, which bind noncovalently to molecules with ITAMs; and on the cytoplasmic side, inhibitory receptors with ITIM(s) which -- upon phosphorylation -- recruit and activate SHP-1 & -2, which inhibit the activating receptors. The balance between activating signals and inhibitory signals is what determines whether a natural killer cell will destroy or bypass a microbe it encounters. ...
Natural killer (NK) cells are innate immune cells that show strong cytolytic function against physiologically stressed cells such as tumor cells and virus-infected cells. NK cells show a broad array of tissue distribution and phenotypic variability. NK cells express several activating and inhibitory receptors that recognize the altered expression of proteins on target cells and control the cytolytic function. NK cells have been used in several clinical trials to control tumor growth. However, the results are encouraging only in hematological malignancies but not very promising in solid tumors. Increasing evidence suggests that tumor microenvironment regulate the phenotype and function of NK cells. In this review, we discussed the NK cell phenotypes and its effector function and impact of the tumor microenvironment on effector and cytolytic function of NK cells. We also summarized various NK cell-based immunotherapeutic strategies used in the past, and the possibilities to improve the function of NK cell
Cytolytic cells of the immune system destroy pathogen-infected cells by polarised exocytosis of secretory lysosomes containing the pore-forming protein perforin. Precise delivery of this lethal hit is essential to ensuring that only the target cell is destroyed. In cytotoxic T lymphocytes (CTLs), this is accomplished by an unusual movement of the centrosome to contact the plasma membrane at the centre of the immunological synapse formed between killer and target cells. Secretory lysosomes are directed towards the centrosome along microtubules and delivered precisely to the point of target cell recognition within the immunological synapse, identified by the centrosome. We asked whether this mechanism of directing secretory lysosome release is unique to CTL or whether natural killer (NK) and invariant NKT (iNKT) cytolytic cells of the innate immune system use a similar mechanism to focus perforin-bearing lysosome release. NK cells were conjugated with B-cell targets lacking major histocompatibility
Cross-sectional studies suggest that moderate physical activity is associated with enhanced resting immune function; however, few randomized controlled trials have investigated this link. We investigated the effect of 12-mo aerobic exercise, relative to stretching control, on in vitro immune function in a randomized, controlled trial of 115 postmenopausal, overweight, or obese sedentary women, aged 50-75 yr. The exercise goal was , or =45 min/day, 5 days/wk. Control women participated in 1 day/wk stretching classes. Immune markers (natural killer cell cytotoxicity, T-lymphocyte proliferation, immune cell counts and phenotypes, and serum immunoglobulins) were assessed at baseline, 3 mo, and 12 mo under strict blood-draw criteria. General estimation equations evaluated intervention effects at 3 and 12 mo, controlling for baseline. Of the 115 women who began the trial, blood samples were available from 109 at 3 mo (95%) and 108 at 12 mo (94%). From baseline to 12 mo, the exercise group participated ...
CD56 is a member of the neural cell adhesion molecule family expressed on cells of the central nervous system and also on NK cells. Previous studies suggest the involvement of CD56 in effector-to-target cell conjugation mediated by NK cells. It was shown recently that CD56 is also expressed by subpopulations of CD8+ and CD4+ T cells. The present study describes the functional characteristics of CD4+CD56+ T cell lines established from blood of multiple sclerosis patients by stimulation with myelin basic protein (MBP). CD4+CD56+, MBP-specific T cell lines were able to lyse MBP-pulsed target cells in an HLA class II-restricted fashion. At the same time, they mediated MHC-unrestricted lysis of CD56+ target cells such as CD56+ lymphoid or glial tumor cells, but not of the typical NK target, K562. A number of experimental results including separation of CD4+CD56+ T cells into CD56 high and low expressing populations, cold target inhibition, as well as killing of CD56-transfected cells indicate that ...
Natural Killer Cells are the most aggressive white cells in the immune system. They make up about 5% to 15% of the total lymphocyte circulating population. They target tumor cell and protect against a wide variety of infectious microbes. Natural Killer Cells are a very important factor in the fight against cancer. Immune Stimulation is the key to keeping the white blood cell count high and giving the Natural Killer Cells a chance to fight cancer and other diseases.. ...
Now, results from a new study carried out using a mouse model, show that modified cells called super natural killer cells are able to seek out cancer cells in lymph nodes to destroy them, thus halting the process of metastasis. Michael King, senior author of the study, said in a press release: We want to see lymph node metastasis become a thing of the past.. The super natural killer cells find the cancerous cells in the lymph nodes and induce apoptosis - in other words, the cancer cells self-destruct and disintegrate, thus averting their further lymphatic spread. But what are these super natural killer cells? They are a modified version of the so-called natural killer cells - or NK cells for short.. NK cells are a type of lymphocytes that play a major role in the killing of cancer cells and virus-infected cells by inducing apoptosis. To obtain the super version of these lymphocytes, scientists attached nanoparticles to the NK cell surface. These nanoparticles contain a protein dubbed TRAIL ...
Natural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stress, such as infection with viruses, bacteria, or parasites or malignant transformation. Although NK cells do not express classical antigen receptors of the immunoglobulin gene family, such as the antibodies produced by B cells or the T cell receptor expressed by T cells, they are equipped with various receptors whose engagement allows them to discriminate between target and nontarget cells. Activating receptors bind ligands on the target cell surface and trigger NK cell activation and target cell lysis. However Inhibitory receptors recognize MHC class I molecules (HLA) and inhibit killing by NK cells by overruling the actions of the activating receptors. This inhibitory signal is lost when the target cells do not express MHC class I and perhaps also in cells infected with virus, which might inhibit ...
Natural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stress, such as infection with viruses, bacteria, or parasites or malignant transformation. Although NK cells do not express classical antigen receptors of the immunoglobulin gene family, such as the antibodies produced by B cells or the T cell receptor expressed by T cells, they are equipped with various receptors whose engagement allows them to discriminate between target and nontarget cells. Activating receptors bind ligands on the target cell surface and trigger NK cell activation and target cell lysis. However Inhibitory receptors recognize MHC class I molecules (HLA) and inhibit killing by NK cells by overruling the actions of the activating receptors. This inhibitory signal is lost when the target cells do not express MHC class I and perhaps also in cells infected with virus, which might inhibit ...
TY - JOUR. T1 - Regulation of IFN-γ production following 2B4 activation in human NK cells. AU - Johnson, Lori A.. AU - Goldfarb, Ronald H.. AU - Mathew, Porunelloor A.. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2000. Y1 - 2000. N2 - IFN-γ is a cytokine that regulates various functions of the immune system. The major producers of IFN-γ are T cells and NK cells. 2B4 is a novel activating receptor expressed on all human NK cells, a subset of CD8+ T cells, monocytes and basophils. Activation of human NK cells through surface 2B4 enhances NK cell cytolytic function and secretion of IFN-γ. We have examined the regulation of IFN-γ production by the human NK cell line YT upon activation through surface 2B4. Our data indicate that ligation of surface 2B4 by mAb C1.7, that specifically recognizes 2B4, induces transcriptional activation of IFN-γ. Partial inhibition of transcription did not prevent the transcriptional upregulation of IFN-γ. S1 nuclease protection ...
Modern subunit vaccines stimulate the B cell immune system and induce neutralizing Abs. However, neutralizing Abs cannot be effective against pathogens that hide intracellularly (e.g., Plasmodium malariae), or that permanently change the antigenic nature of their surface structures (antigenic drift), as is the case with seasonal influenza or HIV. Therefore, there is a need for vaccines utilizing the second powerful arm of the adaptive immune system, the cytotoxic defense (1). In this type of immunity, CD8+ T cells specifically recognize peptide fragments derived from (often conserved) pathogen proteins that are presented on the surface of infected cells in the context of MHC I. As a result, the CD8+ T cells become activated, acquire cytotoxic capacity, and eliminate these infected cells in a highly specific fashion.. Apart from prophylactic vaccination, a therapeutic vaccination employing the cytotoxic potential of the immune system is also needed due to the limitations of current therapies ...
Adoptive cell transfer of tumor infiltrating lymphocytes has shown clinical efficacy in the treatment of melanoma and is now also being explored in other tumor types. Generation of sufficient numbers of effector T cells requires extensive ex vivo expansion, often at the cost of T cell differentiation and potency. For the past 20 years, IL-2 has been the key cytokine applied in the expansion of TIL for ACT. However, the use of IL-2 has also led to collateral expansion of regulatory T cells (Tregs) and progressive T cell differentiation, factors known to limit in vivo persistence and activity of transferred TIL. The use of alternative T cell growth factors is therefore warranted. Here, we have compared the effects of IL-2, -15 and −21 cytokines on the expansion and activation of TIL from single-cell suspensions of non-small cell lung cancer, ovarian cancer and melanoma. We applied the K562-based artificial APC (aAPC) platform for the direct and rapid expansion of tumor infiltrating lymphocytes isolated
The T- and B-Lymphocyte and Natural Killer Cell Profile includes the following tests:. Percentage CD3+; absolute CD3+; percentage CD3+CD4+; absolute CD3+CD4+; percentage CD3+CD8+; absolute CD3+CD8+; percentage CD3-CD56+ natural killer (NK) cells; absolute CD3-CD56+ natural killer (NK) cells; percentage CD19+; absolute CD19+; CD4:CD8 ratio; CBC. .. HIV-1 infection results in a decrease of CD4 T cells, an increase in CD8 T cells, a decrease in the CD4:CD8 ratio, and a progressive destruction of immune function. Enumeration of CD4 and CD8 T cells in HIV-1 seropositive patients may be used for prognostic purposes and to monitor disease progression and retroviral therapy. Natural killer (NK) cells are large granular lymphocytes that mediate MHC-unrestricted cytotoxicity against virus-infected and malignant cells and manufacture a number of cytokines following stimulation of the immune system.. ...
CD8+ T cells play a crucial role in the host defenses against malignancies in both mice and humans (1). The identification of tumor-associated antigens (TAA) recognized by CD8+ T lymphocytes has permitted potentiation of specific immune responses in immunotherapy strategies. Nevertheless, despite the expression of TAAs, tumor eradication by the immune system is often inefficient (2), which accounts for the disappointing clinical activity of most cancer vaccines (3). Extensive studies have shown that tumor cells themselves play a crucial role in modulating the host immune response, such that they maintain their functional disorder and evade immune surveillance (4). In this regard, it has been suggested that tumor cell growth in vivo is not only influenced by cytotoxic T lymphocyte (CTL) tumor cell recognition but also by tumor susceptibility to cell-mediated death (5). While the resistance of tumor cells to T-cell-mediated cytotoxicity remains a major impediment for cancer immunotherapy, its ...
Natural killer (NK) cells comprise 5-20% of peripheral blood mononuclear cells (PBMC) in humans. In addition to their fundamental roles in the defense against viral infections and tumor surveillance, NK cells help shape adaptive immune responses through their production of cytokines. NK cells are traditionally identified as CD3neg, CD14neg, CD19neg lymphocytes expressing CD56. Using a combination of markers that includes CD56 and CD7 greatly increases the ability to define the phenotype and function of NK cell subsets. Two key markers of NK cell function are the production of IFNγ and the release of cytotoxic granules measured by the expression of CD107a. Here we describe a method to assess IFNγ and CD107a expression in NK cells following stimulation with target cells or cytokines. This method can be used to assess the general functional capacity of NK cells in peripheral blood mononuclear cells from a wide range of study participants.
Histidine-rich glycoproteinはCLEC-1Bを介してPD-1発現を調節することでナチュラルキラー細胞活性を増強す ...
Natural killer (NK) cells are a noteworthy lymphocyte subset in cancer adoptive cell therapy. NK cells initiate innate immune responses against infections and malignancies with natural cytotoxicity, which is independent of foreign antigen recognition. Based on these substantive features, genetically modifying NK cells is among the prime goals in immunotherapy but is currently difficult to achieve. Recently, we reported a fully human CAR19 construct (huCAR19) with remarkable function in gene-modified T-cells. Here, we show efficient and stable gene delivery of huCAR19 to primary human NK cells using lentiviral vectors with transduction efficiencies comparable to those achieved with NK cell lines. These huCAR19 NK cells display specific and potent cytotoxic activity against target cells. To improve homing of NK cells to the bone marrow, we augmented huCAR19 NK cells with the human CXCR4 gene, resulting in transgenically augmented CAR NK cells (TRACKs). Compared to conventional CAR NK cells, TRACKs exhibit
The immune system and the nervous system are highly complex organs composed of various different cells that must interact with each other for proper function of the system. This communication can be mediated by soluble factors. The factors released by the nervous system (neurotransmitters) differ from those released by the immune system (cytokines). Nevertheless, the nervous and immune systems can influence each others activity because immune cells express neurotransmitter receptors, and neurons express cytokine receptors. Moreover, immune cells can synthesize and release neurotransmitters themselves, thus using neurotransmitter-mediated pathways via autocrine and paracrine mechanisms. Natural killer (NK) cells are innate lymphocytes that are important for early and effective immune reactions against infections and cancer. Many studies have shown the strong influence of stress and the nervous system on NK cell activity. This phenomenon may be one reason why chronic stress leads to a higher incidence of
Nucleofector™ Kits for Human Natural Killer Cells along with other Nucleofector™ Kits for Primary Blood Cells Products at Lonza.com
BackgroundCD8+ T cells impact control of viral infections by direct elimination of infected cells and secretion of a number of soluble factors. In HIV-1 infection, persistent HIV-1 specific IFN-γ+ CD8+ T cell responses are detected in the setting of disease progression, consistent with functional impairment in vivo. Recent data suggest that impaired maturation, as defined by the lineage markers CD45RA and CCR7, may contribute to a lack of immune control by these responses.Methodology/Principal FindingsWe investigated the maturation phenotype of epitope-specific CD8+ T cell responses directed against HIV-1 in 42 chronically infected, untreated individuals, 22 of whom were
Natural Killer Cells are also defined as large granular lymphocytes (LGL) and comprise the third kind of cells other than B and T Lymphocytes. They usually...
Assay Kits , Cell Proliferation and Cytotoxicity Kits , Sensolyte Cell Cytotoxicity Assay Kit-Larger size; The damage of cell membrane leads to release of cytoplasmic enzymes. The measurement of released cytoplasmic lactate dehydrogenase (LDH) is a well-accepted assay to estimate cell membrane integrity and quantify cytotoxicity. The SensoLyte Cell Cytotoxicity Assay Kit uses resazurin as a sensitive fluorogenic indicator (Ex/Em=560 nm/590 nm upon conversion) to measure LDH activity. The assay can be performed in a mixed population of damaged and viable cells, but only measure the LDH released from damaged cells. The cytoplasmic LDH in living cells produces little signals under assay condition. There is no need of extra steps to separate living cells and supernatant. The fluorescent signal is proportional to the number of damaged cells (up to 2.5X104 cell, r2>0.95) with the detection limit reaching 100 dead cells. The kit is suitable for high throughput screening of
Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the innate immune system. The role NK cells play is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to viral-infected cells, acting at around 3 days aft
The results of the present study extend our previous findings demonstrating that, at diagnosis, patients with locally advanced, HER2-overexpressing BC are characterized by a retained immune proficiency [23], and more importantly, achieve a high rate of pCR (42.5%) after neoadjuvant Trastuzumab and Paclitaxel [35]. These observations, together with the known immune-modulating effects of these drugs [36, 37], prompted us to thoroughly investigate the immune profile of the same cohort of patients along treatment. The time frame in which NC is administered is particularly suitable for immunological studies [36] because it does not suffer from the immune suppression induced by surgery or by advanced metastatic disease.. We herein demonstrate that, in both groups of patients, NC treatment induced significant changes in the relative proportions of circulating immune cells. We first examined what happened within the innate immune compartment, with particular attention to NK cells, given the major role ...
Clone REA227 recognizes rat CD161, a C-type lectin membrane glycoprotein also known as NKR-P1. CD161 is expressed as an 80 kDa disulphide-linked homodimer and is found on most NK cells, T cell subsets, and many dendritic cells. In peripheral blood, CD161 is preferentially expressed on T cells of memory phenotype, but it can also be found on subsets of thymocytes and fetal liver T cells. CD161 has been implicated in triggering NK-mediated cytotoxicity, contributing to target cell recognition by NK cells.Additional information: Clone REA227 displays negligible binding to Fc receptors. - Italia
New research out of the Raulet lab suggests a mechanism explaining why Natural Killer cells are sometimes rendered ineffective, and even more excitingly, suggests a therapeutic approach for re-awakening them to attack tumors. Read more...
Infertility after anti-sperm antibody binding can be caused by autoagglutination, sperm cytotoxicity, blockage of sperm-ovum ... They are protected by other means like immunologic tolerance and immunomodulation. ...
MAbs facilitate destruction of tumor cells by complement-dependent cytotoxicity (CDC) and cell-mediated cytotoxicity (ADCC). In ... Drugs used for immunotherapy can act either passively by enhancing the immunologic response to MET-expressing tumor cells, or ...
... cytotoxicity tests, immunologic MeSH E01.450.495.160.155 - complement hemolytic activity assay MeSH E01.450.495.225 - ... immunologic MeSH E01.450.495.620 - pregnancy tests, immunologic MeSH E01.450.495.735 - serologic tests MeSH E01.450.495.735.050 ... immunologic MeSH E01.450.865.100 - biopsy MeSH E01.450.865.100.100 - biopsy, needle MeSH E01.450.865.100.100.500 - biopsy, fine ... immunologic MeSH E01.370.378.625 - preimplantation diagnosis MeSH E01.370.378.630 - prenatal diagnosis MeSH E01.370.378.630.050 ...
T cell-mediated cytotoxicity.. *Masanori Utsuyama, Junichi Shiraishi, Hiroshi Takahashi, Michiyuki Kasai ja Katsuiku Hirokawa, ... "T-Lymphocytes and Their Receptors in Immunologic Recognition, Immunology", 2. köide, 1988, Harwood Academic Publishers, ...
2010 Primer on Allergic and Immunologic Diseases. 125 (2, Supplement 2): S41-S52. doi:10.1016/j.jaci.2009.09.046. ISSN 0091- ... Complement-dependent cytotoxicity (CDC) is an effector function of IgG and IgM antibodies. When they are bound to surface ... Contrast with antibody-dependent cellular cytotoxicity (ADCC) Schroeder, Harry W.; Cavacini, Lisa (2010). "Structure and ... Zhou 2008 Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan ...
The four known IgG subclasses are involved in antibody-dependent cellular cytotoxicity.Antibodies are a key component of the ... murine molecules were engineered to remove immunogenic content and to increase immunologic efficiency. This was initially ... Major problems associated with murine antibodies included reduced stimulation of cytotoxicity and the formation complexes after ...
In trials these have been a type of T-cell capable of cytotoxicity. Inserting the DNA into the effector cell can be ... This effect has been attributed to making an immunologic space within which the cells populate. The process as a whole results ...
Reilly, C. A., Pritchard, D. J., Biskis, B. O., & Finkel, M. P. (1972). Immunologic evidence suggesting a viral etiology of ... USA). Pritchard, D. J., Reilly, C. A., Finkel, M. P., & Ivins, John C. (1974). Cytotoxicity of human osteosarcoma sera to ...
The degree of cytotoxicity is expressed as percentage PRA (panel reactive antibody). It is a tool that can be employed to ... Mechanisms of immunologic enhancement. Transplant Proc. 1970; 2(1):68-75. Kerman RH, Kimball PM, Van Buren CT, Lewis RM, DeVera ... and Terasaki in 1969 demonstrated the efficacy of complement-dependent lymphocytotoxic cross-match in defining immunologic risk ... HLA antibodies resulting in hyperacute rejection were first detected in 1969 by the complement-dependent cytotoxicity ...
The chronic activation of monocytes can lead to multiple metabolic, hematologic and immunologic abnormalities in patients with ... and increased tumour cell cytotoxicity. The role of M-CSF is not only restricted to the monocyte/macrophage cell lineage. By ...
This process is known as antibody-dependent cell-mediated cytotoxicity (ADCC). FcγRIII on NK cells can also associate with ... Sun PD (2003). "Structure and function of natural-killer-cell receptors". Immunologic Research. 27 (2-3): 539-48. doi:10.1385/ ... Another process involving Fc receptors is called antibody-dependent cell-mediated cytotoxicity (ADCC). During ADCC, FcγRIII ... Immunologic Research. 29 (1-3): 219-30. doi:10.1385/IR:29:1-3:219. PMID 15181284. Sulica A, Chambers WH, Manciulea M, Metes D, ...
Immunoglobulin light chain Immunoglobulin M Immunoglobulin Y Immunohaematology Immunoisolate Immunologic activation Immunologic ... CXCL16 CXCL17 CXCL2 CXCL3 CXCL5 CXCL6 CXCL7 CXCL9 CXCR4 CXCR6 CXCR7 Cytokine Cytokine redundancy Cytokine storm Cytotoxicity ... Anti-cholesterol Anti-gliadin antibodies Antibody Antibody opsonization Antibody-dependent cell-mediated cytotoxicity Antibody- ...
Sun PD (2003). "Structure and function of natural-killer-cell receptors". Immunologic Research. 27 (2-3): 539-48. doi:10.1385/ ... This process is known as antibody-dependent cell-mediated cytotoxicity (ADCC). FcγRIII on NK cells can also associate with ... Induction of antibody-dependent cell-mediated cytotoxicity (ADCC). Induction of cytokine release by macrophages ... or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as ...
Impaired NK-cell cytotoxicity is the hallmark of HLH. All genetic defects for familial HLH are related to granule-dependent ... immunologic abnormalities, and lymphohistiocytosis. Most cases have been diagnosed between 4 months and 7 years of age, with a ... occurs after strong immunologic activation, such as that which can occur with systemic infection, immunodeficiency, or ... cytotoxicity. This inability to remove infected and antigen-presenting cells and terminate the immune response leads to ...
A path for definitive treatment for XLPDR is at present unclear, but it is tempting to speculate whether the immunologic ... discovered that POLA1 deficiency is associated with decreased direct cytotoxicity of NK cells due to disturbances in vesicular ... Meanwhile, antibody-dependent cell cytotoxicity (ADCC) remains unchanged in XLPDR NK cells. The most common manifestations of ... and impaired direct cytotoxicity of NK cells are the most common symptoms. In females the disease is characterized by skin ...
This effect has been attributed to making an immunologic space within which the cells populate.[52] The process as a whole ... In trials these have been a type of T-cell capable of cytotoxicity.[53] ...
... and CR3-dependent cellular cytotoxicity. Complement-dependent cytotoxicity occurs when antibodies bind to the cancer cell ... T cells and immune system cytokines and have been investigated in clinical trials as immunologic adjuvants. Many tumors express ... Complement can lead to cell death by activation of the membrane attack complex, known as complement-dependent cytotoxicity; ... The antibody's mode of action is primarily through the induction of ADCC and complement-mediated cytotoxicity. Other mechanisms ...
Increase of the cytotoxicity of anticancer drugs". Biochemical Pharmacology. 37 (24): 4727-33. doi:10.1016/0006-2952(88)90344-9 ... June 2019). "High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell ...
Paliwal S; Sundaram, J; Mitragotri, S. Induction of cancer-specific cytotoxicity towards human prostate and skin cells using ... phytochemicals and vitamins and their immunologic effects. The Journal of allergy and clinical immunology. 2009, 123 (2): 283- ...
84(10):1215-9 - according to Sánchez-Fueyo A, Strom TB (2011), Immunologic basis of graft rejection and tolerance following ... Increased natural cytotoxicity receptor expression and relevant IL-10 production in NK cells from chronically infected viremic ... Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs. Gastroenterology ...
The Fc portion of rituximab mediates antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC ... "Immunologic and Clinical Responses to Rituximab in a Child With Opsoclonus-Myoclonus Syndrome". Pediatrics. 115 (1): e115-e119 ... Rituximab mechanisms of action; the three major independent mechanisms are (1) antibody dependent cellular cytotoxicity (ADCC ... antibody-dependent cellular cytotoxicity).[55] This strategy for enhancing a monoclonal antibody's ability to induce ADCC takes ...
Rus H, Cudrici C, Niculescu F (2005). "The role of the complement system in innate immunity". Immunologic Research. 33 (2): 103 ... The "knobs-into-holes" shape facilitates antibody dependent cell mediated cytotoxicity. Single chain variable fragments (scFv) ... Immunologic Research. 36 (1-3): 27-32. doi:10.1385/IR:36:1:27. PMID 17337763. S2CID 27041937. Pier GB, Lyczak JB, Wetzler LM ( ... of natural killer cells by antibodies initiates a cytotoxic mechanism known as antibody-dependent cell-mediated cytotoxicity ( ...
1996). "Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41". Science. 274 (5294): 1917-21. ... causes increased sensitivity to cytotoxicity and early embryonic lethality". Proceedings of the National Academy of Sciences of ... They defined the role for NO generated from neuronal NO synthase or immunologic NO synthase leads in models of HIV dementia and ...
Deretic, V; Kimura, T; Timmins, G; Moseley, P; Chauhan, S; Mandell, M (Jan 2015). "Immunologic manifestations of autophagy". J ... "Elevated furin levels in human cystic fibrosis cells result in hypersusceptibility to exotoxin A-induced cytotoxicity". The ...
... the epitope can be recognized by immunologic structures like T-cell receptors (TCRs). The molecular region which binds to the ... causing damage via mechanisms such as direct cytotoxicity from CD8 cells. Acute humoral rejection and chronic disfunction ...
Czaja AJ, Carpenter HA, Santrach PJ, Moore SB (January 1995). "Immunologic features and HLA associations in chronic viral ... whereas class I mediated cytotoxicity is not. MICA and MICB are intestinally expressed. There are many genes that lie on either ...
... because it acts as DAMPs after its release to extracellular space of cells in the context of immunologic not-silent cell death ... enhances Fas ligand-mediated cytotoxicity of murine T helper 1 cells". Cellular Immunology. 173 (2): 230-5. doi:10.1006/cimm. ...
The Dawsons showed that NO derived from neuronal NO synthase and immunologic NO synthase leads to degeneration of dopamine ... 2004). "Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality". Proc ...
Pranzatelli M. R. (2004)։ «Immunologic and Clinical Responses to Rituximab in a Child with Opsoclonus-Myoclonus Syndrome»։ ... a polarization of B cells that augments its therapeutic function in NK-cell-mediated antibody-dependent cellular cytotoxicity ...
... members of the immunoglobulin superfamily play fundamental roles in intercellular recognition involved in various immunologic ...
However, these same events can lead to an inflammatory process in genetically predisposed individuals when the immunologic ... Avenins cytotoxicity in celiac people depends on the oat cultivar consumed because of prolamin genes, protein amino acid ...
... depending on the immunologic reactivity of their polysaccharide capsule.[1][4][5] This is why the plural term group B ... of Streptococcus urinary tract infection depends on bacterial strain and β-hemolysin/cytolysin that mediates cytotoxicity, ...
They also suggested that the presence of neutralizing antibody or antibody-dependent cellular cytotoxicity-mediating antibodies ... March 2005). "Correlation between immunologic responses to a recombinant glycoprotein 120 vaccine and incidence of HIV-1 ...
Immunologic" by people in this website by year, and whether "Cytotoxicity, Immunologic" was a major or minor topic of these ... "Cytotoxicity, Immunologic" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... Below are the most recent publications written about "Cytotoxicity, Immunologic" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Cytotoxicity, Immunologic". ...
Natural Killer Cell Cytotoxicity, soluble CD8, and the cytotoxic subset of CD8 cells. There were no changes in HIV disease ... we identify an essential role for IGF-1 in the positive regulation of human natural killer cell development and cytotoxicity. ... cells have the ability to produce IGF-1 and that differential endogenous IGF-1 expression leads to disparate cytotoxicity in ... stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity ...
Immunologic cytotoxicity; Natural killer cell replacementsNACID 103CASI PharmaceuticalsIAntibody-dependent cell cytotoxicity; ... T lymphocyte replacementsImmunologic cytotoxicity; Natural killer cell replacements By Targets Protease Multiple Kinase By ... Proto-oncogene protein c-bcl-2 inhibitorsOralRG6160GenentechIAntibody-dependent cell cytotoxicity; T lymphocyte ... T lymphocyte stimulantsParenteralRAPA-201 Autologous T cellsRapa TherapeuticsIIImmunologic cytotoxicity; T lymphocyte ...
el); gren af biomedicin (da) Immunologico (it); Immunologique, Immunobiologie (fr); Inmunologia (eu); Immunològica, ...
Antibody-Dependent Cell Cytotoxicity * Cyclic AMP / blood * Cyclic GMP / blood * Cytotoxicity, Immunologic ... The antibody-dependent cellular cytotoxicity (ADCC) was also impaired with ageing in both sexes. The age-dependent decrease in ...
Cytotoxicity, Immunologic. Acute Infection. Additional relevant MeSH terms: Infection. HIV Infections. Acquired ... Immunologic Deficiency Syndromes. Immune System Diseases. Slow Virus Diseases. Lamivudine. Zidovudine. Lamivudine, zidovudine ... To determine the patterns of immunologic activation as measured by cell surface marker levels, soluble and cell-associated ...
Cytotoxicity, Immunologic. *Female. *Immunity, Cellular. *Listeria monocytogenes. *Listeria monocytogenes: immunology. * ...
... contributes to the inhibitory activity of MOPC-315 culture supernatants for the in vitro generation of antitumor cytotoxicity ... Cytotoxicity, Immunologic * Dose-Response Relationship, Drug * Female * Immunocompromised Host * Interferon-gamma / metabolism ... did not lead to enhancement in the in vitro generation of antitumor cytotoxicity. The cessation of IL-10 secretion as a ... infiltrated spleens of mice bearing a large MOPC-315 tumor resulted in the generation of enhanced anti-MOPC-315 cytotoxicity. ...
Identification by morphologic and immunologic criteria. J Clin Invest 1973; 52: 2745-56.. *CrossRef, ... Quan, H., Xu, Y. and Lou, L. (2008), p38 MAPK, but not ERK1/2, is critically involved in the cytotoxicity of the novel vascular ... p38 MAPK, but not ERK1/2, is critically involved in the cytotoxicity of the novel vascular disrupting agent combretastatin A4. ...
Requirements for CD28-dependent T cell-mediated cytotoxicity. J Immunol.1993;150 (6):2091- 2101. ... Booster Vaccinations: Can Immunologic Memory Outpace Disease Pathogenesis? Message Subject (Your Name) has sent you a message ... Immunologic memory in Haemophilus influenzae type b conjugate vaccine failure. Arch Dis Child.2003;88 (5):379- 383. ... A decrease in antibody despite persistence of immunologic memory was associated with a decline in vaccine effectiveness.44-46 ...
Immunologic cytotoxicity. Immunocompetence. Immunologic factors (General)". Up a level. Export as ASCII Citation. BibTeX. ...
Glomerulonephritis • Renal Dialysis • Vaccination • Cytotoxicity, Immunologic • HLA Antigens • Pneumoconiosis • Textile ...
Cytotoxicity, Immunologic. *Chromosome 12. *Polymerase Chain Reaction. *T-Cell Antigen Receptors. *Cell Proliferation ... Finally, complement-dependent cytotoxicity assay showed that anti-CD70 antibody mediated effective complement-dependent killing ... AZD1775 targets the cell cycle checkpoint kinase Wee1 and potentiates genotoxic agent cytotoxicity through p53-dependent or - ... Importantly, inhibition of MYD88 signaling induced cytotoxicity and inhibited cell growth of cell lines issued from patients ...
Cytotoxicity Tests, Immunologic. Cytotoxicity, Immunologic*. Humans. Immunosuppressive Agents / therapeutic use. Isoantigens / ...
Cytotoxicity, Immunologic. Dose-Response Relationship, Drug. Graft Survival. Immunosuppression / methods*. Isoantibodies / ...
2010 Primer on Allergic and Immunologic Diseases. 125 (2, Supplement 2): S41-S52. doi:10.1016/j.jaci.2009.09.046. ISSN 0091- ... Complement-dependent cytotoxicity (CDC) is an effector function of IgG and IgM antibodies. When they are bound to surface ... Contrast with antibody-dependent cellular cytotoxicity (ADCC) Schroeder, Harry W.; Cavacini, Lisa (2010). "Structure and ... Zhou 2008 Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan ...
Cytotoxicity Tests, Immunologic. The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator ...
The etiology and immunologic states of autoimmune diseases have mainly been discussed without consideration of extrathymic T ... Miyaji C, Watanabe H, Miyakawa R, et al.: Identification of effector cells for TNFα-mediated cytotoxicity against WEHI164S ... The etiology and immunologic states of autoimmune diseases have mainly been discussed without consideration of extrathymic T ... The immunologic states of autoimmune diseases resemble those of aging, chronic GVH disease, and malarial infection. Namely, ...
Immunologic cytotoxicity; Natural killer cell replacementsNACID 103CASI PharmaceuticalsIAntibody-dependent cell cytotoxicity; ... T lymphocyte replacementsImmunologic cytotoxicity; Natural killer cell replacements By Targets Protease Multiple Kinase By ... Proto-oncogene protein c-bcl-2 inhibitorsOralRG6160GenentechIAntibody-dependent cell cytotoxicity; T lymphocyte ... T lymphocyte stimulantsParenteralRAPA-201 Autologous T cellsRapa TherapeuticsIIImmunologic cytotoxicity; T lymphocyte ...
Cytotoxicity, Immunologic. 3. 2017. 1546. 0.160. Why? Blotting, Western. 3. 2016. 6027. 0.160. Why? ... Suppressor Factors, Immunologic. 1. 2012. 73. 0.140. Why? Reverse Transcriptase Polymerase Chain Reaction. 2. 2016. 5362. 0.140 ...
Percentage of specific cytotoxicity was calculated conventionally.. TNF-β release was detected by measuring the cytotoxicity of ... Confocal microscopy analysis of immunologic synapse assembly. Tumor cells and CTLs were cocultured for 30 minutes at a 1:2 ... Cytotoxicity experiments and TNF-β production assay. The cytotoxic activity of the CTL clone was measured by a conventional 4- ... A, cytotoxicity was determined by a conventional 4-hour 51Cr release assay at different ratios. Heu33 cells were used as ...
Burlingham, W.J. and D. Steinmuller (1983). Cell-mediated cytotoxicity to nonmajor histocompatibility complex alloantigens on ... Sakaguchi, S., N. Sakaguchi, M. Asano, M. Itoh, and M. Toda (1995). Immunologic self-tolerance maintained by activated T cells ... Burlingham W.J., Torrealba J. (2004) Immunologic Tolerance as Taught by Allografts. In: Wilkes D.S., Burlingham W.J. (eds) ... 1992). The effect of donor age, recipient age, and HLA match on immunologic graft survival in cadaver renal transplant ...
Categories: Cytotoxicity, Immunologic Image Types: Photo, Illustrations, Video, Color, Black&White, PublicDomain, ...
Antibody-Dependent Cell Cytotoxicity; Antibodies, Monoclonal; Humanized; Immunologic Factors; Killer Cells, Natural; ... Title: SO-C101 induces NK cell cytotoxicity and potentiates antibody-dependent cell cytotoxicity and anti-tumor activity. ...
2003) The mature activating natural killer cell immunologic synapse is formed in distinct stages. Proc Natl Acad Sci USA 100: ... is indispensable for NK cell cytotoxicity. WIP knockdown completely inhibited cytotoxicity, whereas overexpression of WIP ... Assessment of YTS cytotoxicity was repeated and expanded by the analysis of the effects of WIP overexpression in YTS cells and ... WIP has been shown to be involved in NK cell cytotoxicity. WIP knockdown in the NK tumor cell line YTS impaired its ability to ...
The ABCs of granule-mediated cytotoxicity: new weapons in the arsenal. Nat. Rev. Immunol. 3: 361-370. ... Combination Therapy with Anti-CTLA-4 and Anti-PD-1 Leads to Distinct Immunologic Changes In Vivo. Rituparna Das, Rakesh Verma, ... Combination Therapy with Anti-CTLA-4 and Anti-PD-1 Leads to Distinct Immunologic Changes In Vivo ... Combination Therapy with Anti-CTLA-4 and Anti-PD-1 Leads to Distinct Immunologic Changes In Vivo ...
Immunologic Research 29:081-092.. https://doi.org/10.1385/IR:29:1-3:081 * Google Scholar ... NK cytotoxicity assay. Request a detailed protocol NK cells were enriched from spleen cells of the indicated mice by negative ... A herpesvirus encoded Qa-1 mimic inhibits natural killer cell cytotoxicity through CD94/NKG2A receptor engagement. ... NK cytotoxicity can be inhibited by the engagement of CD94/NKG2A with its ligand Qa-1 and this inhibitory effect is highly ...
Cytotoxicity, Immunologic (immunology) *Drug Resistance, Neoplasm. *Female. *Gangliosides (genetics, immunology) *Genetic ...
The mature activating natural killer cell immunologic synapse is formed in distinct stages. Proc Natl Acad Sci U S A. 2003;100( ... of NK cytotoxicity (38). In agreement with this, we observed that anti-CD2 mAb significantly reduced CD16.NK-92 cytotoxicity ... Human CD16 as a lysis receptor mediating direct natural killer cell cytotoxicity. Proc Natl Acad Sci U S A. 1999;96(10):5640- ... Cytotoxicity assays. NK-92, CD16.NK-92, and CD16.L66H.NK-92 cells and PBMCs were used as effectors against 51Cr-labeled K562, ...
  • Persistence of vaccine-induced antibodies usually goes well beyond the time when they should have decayed to undetectable levels because of ongoing "natural" boosting or other immunologic mechanisms. (aappublications.org)
  • Complement-dependent cytotoxicity (CDC) is an effector function of IgG and IgM antibodies. (wikipedia.org)
  • Loss of specific natural cell-mediated cytotoxicity with absorption of natural antibodies from serum. (springer.com)
  • In this form of cytotoxicity, effector cells with receptors for the Fc portion of immunoglobulin produce target cell lysis by attachment to the Fc portion of antibodies that are bound to target cells via their antigen‐combining sites. (currentprotocols.com)
  • However, the antibodies raised against the native toxins were more inhibitory to the C. perfringens- induced cytotoxicity (as tested on bovine endothelial cells) and only these antibodies protected against C. perfringens challenge in the intestinal loop model. (biomedcentral.com)
  • 17 One of potential roles of these antigens is the protection of trophoblasts from cytotoxicity. (nih.gov)
  • Although activation of natural killer (NK) cytotoxicity is generally inhibited by target major histocompatibility complex (MHC) class I expression, subtle features of NK allorecognition suggest that NK cells possess receptors that are activated by target MHC I. The mouse Ly-49D receptor has been shown to activate NK cytotoxicity, although recognition of MHC class I has not been demonstrated previously. (nih.gov)
  • One pathway of NK cell activation involves the engagement of activating cytotoxicity receptors through inducible ligands on target cells. (aacrjournals.org)
  • Cytotoxicity, Immunologic" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (uchicago.edu)
  • The current studies demonstrate that MOPC-315 tumor cells secrete large amounts of interleukin-10 (IL-10), which contributes to the inhibitory activity of MOPC-315 culture supernatants for the in vitro generation of antitumor cytotoxicity by MOPC-315-"immune" spleen cells. (nih.gov)
  • Moreover, addition of neutralizing monoclonal anti-IL-10 antibody to the in vitro stimulation cultures of cells from the tumor infiltrated spleens of mice bearing a large MOPC-315 tumor resulted in the generation of enhanced anti-MOPC-315 cytotoxicity. (nih.gov)
  • L-PAM) therapy (and whose spleens no longer contain metastatic tumor cells) did not lead to enhancement in the in vitro generation of antitumor cytotoxicity. (nih.gov)
  • Mouse peritoneal macrophages activated for tumor cytotoxicity by any of several in vivo or in vitro treatments released a soluble cytotoxin into culture fluids only after exposure to small amounts of bacterial lipopolysaccharides. (uni-regensburg.de)
  • These in vitro assays screened for the ability of the adjuvant to bind to mucin, induce cytotoxicity, facilitate antigen uptake in epithelial and dendritic cells, and activate cellular pathways. (plos.org)
  • In an in vitro study, ethanol extract of boneset leaves showed potent cytotoxicity with EC 50 of 12-14microg/mL and weak antibacterial activity against Gram-positive bacteria ( Staphylococcus aureus and Bacillus megaterium ). (sigmaaldrich.com)
  • 1999 ). Recently, unique immunologic properties of MSCs have been described, such as their poor immunogenicity in vitro and in vivo (Klyushnenkova et al. (pubmedcentralcanada.ca)
  • These macrophages also failed to demonstrate cytotoxicity to tumor cells in vitro, a defined nonspecific effector function of activated macrophages. (ajtmh.org)
  • The high avidity format is also superior in in vitro NK-mediated tumor cell targeting as shown in cytotoxicity assays. (aacrjournals.org)
  • 10 11 12 13 14 15 Because of the parallel findings of these reports, many assumed that the assessment of circulating TNF by the cytotoxicity assays would be highly correlated with its measurement by the immunologic assays, since the results of these assays are highly correlated in vitro when known quantities of recombinant TNF are added to culture media. (ahajournals.org)
  • Third, the secretion of TNF in vivo might be accompanied by the release of endogenously produced antagonists, which would interfere with the in vitro cytotoxicity but not the antigenicity of the cytokine. (ahajournals.org)
  • The antibody-dependent cellular cytotoxicity (ADCC) was also impaired with ageing in both sexes. (nih.gov)
  • Contrast with antibody-dependent cellular cytotoxicity (ADCC) Schroeder, Harry W. (wikipedia.org)
  • We analyzed peripheral blood mononuclear cells (PBMCs) and matched melanoma metastases from 15 patients responding and 14 not responding to ipilimumab by multicolor flow cytometry, antibody-dependent cell-mediated cytotoxicity (ADCC) assay, and immunohistochemistry. (pnas.org)
  • This phenomenon, recently reviewed by Perlmann , Perlmann , and Wigzell (1972), was first described by Möller in 1965 and has received a number of designations, including antibody-dependent cell-mediated (or cellular) cytotoxicity (ADCC), antibody-dependent lymphocyte cytotoxicity (ADLC), cell dependent antibody-mediated cytotoxicity (CDAMC), and lymphocyte-dependent antibody (LDA). (springer.com)
  • For the purpose of this review, this immunologic reaction will be referred to as ADCC. (springer.com)
  • Antibody‐dependent cell‐mediated cytotoxicity (ADCC) is an immunologic cytotoxic effector mechanism that is dependent on the cooperative interaction of humoral and cellular effector elements. (currentprotocols.com)
  • Immune-effects mediated by the Fc domain include antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and complement-dependent cytotoxicity (CDC) (Nimmerjahn and Ravetch 2010). (deepdyve.com)
  • Antibody-dependent cellular cytotoxicity to a syngeneic gross virus-induced lymphoma. (springer.com)
  • A phase 1 study of IL-12 in combination with rituximab was conducted in 43 adults with B-cell lymphoma to determine the optimal immunologic dose of this combination. (bloodjournal.org)
  • However, macrophages from BCG-treated mice were significantly more resistant to initial infection with L. tropica , killed intracellular amastigotes by 72 hours in culture and were cytotoxic to tumor cells, indicating full immunologic activation. (ajtmh.org)
  • Patients also have very severe immune abnormalities, principaly characterized by a defect in cytotoxicity and onset of uncontrolled T cells and macrophages proliferation, which infiltrate the various organs. (eurekalert.org)
  • The methyl thiazolyl tetrazolium (MTT) assay was used to assess the cytotoxicity of these materials for human gingival fibroblasts (HGFs). (fluoridealert.org)
  • A novel flow cytometric assay for evaluating cell-mediated cytotoxicity. (molecularstation.com)
  • Cytotoxicity of BV was measured using a CellTiter-96® aqueous cell proliferation assay kit. (blogspot.com)
  • The first study of elevated circulating levels of tumor necrosis factor in heart failure used a cytotoxicity assay to measure concentrations of the cytokine. (ahajournals.org)
  • Second, the cytotoxicity assay might measure substances that share the cytotoxic properties of TNF but are antigenically distinct. (ahajournals.org)
  • However, none of the patients with elevated levels of antigenic TNF showed elevated levels of biologically active TNF (as assessed by a cytotoxicity assay). (ahajournals.org)
  • To determine if basiliximab enhances the magnitude or character of pp65-specific vaccine-induced cellular or humoral immune responses, inhibits or enhances activation-induced cell death, or induces immunologic or clinical evidence of autoimmunity. (clinicaltrials.gov)
  • All patients will undergo leukapheresis again for DC generation and immunologic monitoring with specific assessment of baseline antigen-specific cellular and humoral immune responses 3 + 1 weeks after vaccine #3. (clinicaltrials.gov)
  • Cell-mediated cytotoxicity, allograft rejection and tumor immunity. (springer.com)
  • Our findings establish reduced cytotoxicity as a key mechanism by which tumor PD-L1 suppresses antitumor immunity and demonstrate that tumor PD-L1 is not just a marker of suppressed antitumor immunity. (rupress.org)
  • Thus, 15 years after the first description of the detection of HIV-specific T helper cells in seronegative individuals, the 'immunologic advantage' possibly conferring resistance to HIV infection can be summarized as being correlated with the elicitation of systemic and mucosal cell-mediated immunity, presumably within favorable genetic and innate immunity settings. (lww.com)
  • Zhou 2008 Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling. (wikipedia.org)
  • This study suggests a potential mechanism of action of ipilimumab (a fully human anti-cytotoxic T lymphocyte-associated antigen 4), by which FcγRIIIA (CD16)-expressing nonclassical monocytes kill regulatory T cells ex vivo via antibody-dependent cell-mediated cytotoxicity. (pnas.org)
  • Antibody in the sera of tumorbearing mice that mediates spleen cell cytotoxicity toward autologous tumor. (springer.com)
  • Lymphoid cell- mediated antibody-dependent cytotoxicity in untreated and bursectomized chickens. (springer.com)
  • Characterization of human lymphoid cell-mediated antibody-dependent cytotoxicity (LDAC). (springer.com)
  • The role of antibody-dependent cell-mediated cytotoxicity in renal allograft rejection. (springer.com)
  • Infertility after anti-sperm antibody binding can be caused by autoagglutination, sperm cytotoxicity, blockage of sperm-ovum interaction, and inadequate motility. (wikipedia.org)
  • 4,5 It has been suggested that lenalidomide increases antibody-dependent, cell-mediated cytotoxicity and thus decreases tumor-induced resistance. (freecme.com)
  • Lymphocyte cytotoxicity induced by preincubation with serum from patients with Hashimoto thyroiditis. (springer.com)
  • Lymphocyte cytotoxicity for kidney cells in renal tubular acidosis of autoimmune liver disease. (ebscohost.com)
  • In the absence of further reduction of insulin-receptor membrane display, neither the mixed-lymphocyte culture nor lymphocyte-mediated cytotoxicity reaction was affected. (diabetesjournals.org)
  • The reactive oxygen species produced by gG-2p20-activated phagocytes both inhibited NK cell cytotoxicity and accelerated the apoptotic cell death in NK cell-enriched lymphocyte populations. (gu.se)
  • WIP knockdown completely inhibited cytotoxicity, whereas overexpression of WIP enhanced NK cell cytolytic ability. (pnas.org)
  • 1992). The effect of donor age, recipient age, and HLA match on immunologic graft survival in cadaver renal transplant recipients. (springer.com)
  • The morphology, viability, apoptosis, cytotoxicity (killing tumor cell activity) and cytokine and cytolytic proteins secretion of NK cells were evaluated respectively. (fda.gov)
  • Bedi, A. Resistance of cancers to immunologic cytotoxicity and adoptive immunotherapy via X-linked inhibitor of apoptosis protein expression and coexisting defects in mitochondrial death signaling. (hopkinsmedicine.org)
  • Specifically, we show that human natural killer cells have the ability to produce IGF-1 and that differential endogenous IGF-1 expression leads to disparate cytotoxicity in human primary natural killer cells. (isharonline.org)
  • The etiology and immunologic states of autoimmune diseases have mainly been discussed without consideration of extrathymic T cells, which exist in the liver, intestine, and excretion glands. (springer.com)
  • Because extrathymic T cells are autoreactive and are often simultaneously activated along with autoantibody-producing B-1 cells, these extrathymic T cells and B-1 cells should be introduced when considering the immunologic states of autoimmune diseases. (springer.com)
  • These facts suggest that the immunologic states of autoimmune diseases should be revaluated by introducing the concept of extrathymic T cells and autoantibody-producing B-1 cells, which might be primordial lymphocytes in phylogeny. (springer.com)
  • Cell-mediated cytotoxicity to nonmajor histocompatibility complex alloantigens on mouse epidermal cells. (springer.com)
  • Microarray and qRT-PCR data analyses showed significant upregulation of some cytotoxicity-related genes, including those from the granzyme family, tumor necrosis factor, Fas Ligand, and chemokines, in the spleen cells of IFNg KO mice. (hindawi.com)
  • To determine if basiliximab alters the phenotype (CD56 expression), cytokine secretion profile, or cytotoxicity of CD3-CD56+ natural killer cells. (clinicaltrials.gov)
  • Natural killer (NK) cells play a pivotal role in human immunologic surveillance. (fda.gov)
  • 2005 ), inhibition of the proliferation and cytotoxicity of natural killer (NK) cells (Spaggiari et al. (pubmedcentralcanada.ca)
  • Results: CNS melanomas were more tolerogenic than equivalently progressed tumors outside the CNS as antigen-specific CD8 T cells were deleted and exhibited impaired cytotoxicity. (aacrjournals.org)
  • Results were duplicated across cell lines representing microsatellite instability, CpG island methylator, and chromosomal instability phenotypes, suggesting immunologic elimination of cells expressing these proteins could impact the progression of all CRC phenotypes. (aacrjournals.org)
  • Below are the most recent publications written about "Natural Cytotoxicity Triggering Receptor 1" by people in Profiles. (umassmed.edu)
  • It is concluded that those immunologic activities of lymphocytes that can be modulated by insulin are affected by regulation of insulin-receptor display on activated lymphocytes. (diabetesjournals.org)
  • Therefore, receptor regulation is not effete but carries significant immunologic consequence. (diabetesjournals.org)
  • This study supports the hypothesis that insulin-directed immunologic activity is regulated at the site of receptor display rather than at the locus of regulation of the ligand itself. (diabetesjournals.org)
  • These data show a high throughput approach to the identification of biologically relevant putative immunologic targets for CRC and identified three candidates suitable for vaccine development. (aacrjournals.org)
  • Patients will have blood drawn for immunologic monitoring before basiliximab infusions and prior to vaccines 1, 2, 3, and prior to monthly vaccines and then bimonthly through TMZ cycles without receiving any other prescribed antitumor therapy until progression. (clinicaltrials.gov)
  • 6 Such an immunologic effect may potentially enhance the antitumor activity of rituximab. (freecme.com)
  • Here, we identify an essential role for IGF-1 in the positive regulation of human natural killer cell development and cytotoxicity. (isharonline.org)
  • Here, we demonstrate that Wiskott-Aldrich syndrome protein (WASp)-interacting protein (WIP), important in generation of a large complex of proteins involved in actin cytoskeleton rearrangements, is indispensable for NK cell cytotoxicity. (pnas.org)
  • Mouse Ly-49D recognizes H-2Dd and activates natural killer cell cytotoxicity. (nih.gov)
  • MC38-derived PD-L1 potently inhibited CD8 + T cell cytotoxicity. (rupress.org)
  • The investigators have identified a pervasive deficit in natural killer (NK) cell cytotoxicity in WAS patients. (knowcancer.com)
  • Immunologic reconstitution following hematopoietic stem cell transplantation despite lymph node paucity in NF-?B-inducing kinase deficiency. (childrenshospital.org)
  • Comprehensive evaluation of cell-mediated cytotoxicity is very important, especially in the clinical setting, when a surrogate immunologic endpoint that. (molecularstation.com)
  • To characterize immunologic cell infiltrate in recurrent tumors and seek evidence of antigen-escape outgrowth. (clinicaltrials.gov)
  • Habtemariam, S. and Macpherson, A. M. Cytotoxicity and antibacterial activity of ethanol extract from leaves of a herbal drug, boneset (Eupatorium perfoliatum). (sigmaaldrich.com)
  • Additionally, a treatment regimen using focal radiation therapy and recombinant Listeria monocytogenes was evaluated for immunologic activity and efficacy in this model. (aacrjournals.org)
  • This graph shows the total number of publications written about "Cytotoxicity, Immunologic" by people in this website by year, and whether "Cytotoxicity, Immunologic" was a major or minor topic of these publications. (uchicago.edu)
  • The immunologic states of autoimmune diseases resemble those of aging, chronic GVH disease, and malarial infection. (springer.com)
  • These data demonstrate that, despite shared property of checkpoint blockade, Abs against PD-1, CTLA-4 alone, or in combination have distinct immunologic effects in vivo. (jimmunol.org)
  • They are protected by other means like immunologic tolerance and immunomodulation. (wikipedia.org)
  • The optimal immunologic dose of IL-12 in combination with rituximab was determined to be 300 ng/kg subcutaneously twice weekly starting on day 2. (bloodjournal.org)
  • It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. (umassmed.edu)
  • 2010 Primer on Allergic and Immunologic Diseases. (wikipedia.org)
  • BV appears to be relatively safe, and is of potential value for the treatment of airway inflammation and/or immunologic diseases. (blogspot.com)
  • Cytotoxicity of sodium fluoride on human oral mucosal fibroblasts and its mechanisms. (fluoridealert.org)