Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint.Epitopes: Sites on an antigen that interact with specific antibodies.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.Mice, Inbred BALB CCross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Antibodies, Neutralizing: Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.Antibody Affinity: A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.Caspases: A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Binding Sites, Antibody: Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.Death: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Antigens, Surface: 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.Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry.Antibodies, Anti-Idiotypic: Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Neutralization Tests: The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).Immunoglobulin Fab Fragments: Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Antibodies, Neoplasm: Immunoglobulins induced by antigens specific for tumors other than the normally occurring HISTOCOMPATIBILITY ANTIGENS.Cell Line, Tumor: A cell line derived from cultured tumor cells.Necrosis: 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.Flow Cytometry: 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.Caspase 3: 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.Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Antibodies, Monoclonal, Humanized: Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.Antigens, Neoplasm: 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.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Proto-Oncogene Proteins c-bcl-2: 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.Molecular Weight: The sum of the weight of all the atoms in a molecule.DNA Fragmentation: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Immunoglobulin M: A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.T-Lymphocytes: 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.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.HIV Antibodies: Antibodies reactive with HIV ANTIGENS.Mitochondria: 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)Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Autophagy: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.Mice, Inbred C57BLRabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.In Situ Nick-End Labeling: An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.Antigens, CD95: 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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.Death, Sudden, Cardiac: Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)Antibodies, Protozoan: Immunoglobulins produced in a response to PROTOZOAN ANTIGENS.Antibodies, Antinuclear: Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.Antigens, CD: 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.Immunization, Passive: Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.bcl-2-Associated X Protein: A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Immunosorbent Techniques: Techniques for removal by adsorption and subsequent elution of a specific antibody or antigen using an immunosorbent containing the homologous antigen or antibody.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Enzyme Activation: 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.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Antigens: Substances that are recognized by the immune system and induce an immune reaction.Antibodies, Fungal: Immunoglobulins produced in a response to FUNGAL ANTIGENS.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Fluorescent Antibody Technique, Indirect: A form of fluorescent antibody technique commonly used to detect serum antibodies and immune complexes in tissues and microorganisms in specimens from patients with infectious diseases. The technique involves formation of an antigen-antibody complex which is labeled with fluorescein-conjugated anti-immunoglobulin antibody. (From Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Brain Death: A state of prolonged irreversible cessation of all brain activity, including lower brain stem function with the complete absence of voluntary movements, responses to stimuli, brain stem reflexes, and spontaneous respirations. Reversible conditions which mimic this clinical state (e.g., sedative overdose, hypothermia, etc.) are excluded prior to making the determination of brain death. (From Adams et al., Principles of Neurology, 6th ed, pp348-9)Kinetics: The rate dynamics in chemical or physical systems.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Immunoassay: A technique using antibodies for identifying or quantifying a substance. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance.Antibodies, Monoclonal, Murine-Derived: Antibodies obtained from a single clone of cells grown in mice or rats.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Immunologic Techniques: Techniques used to demonstrate or measure an immune response, and to identify or measure antigens using antibodies.Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.Lymphocyte Activation: 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.Fas Ligand Protein: 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.Amino Acid Chloromethyl Ketones: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Apoptosis Regulatory Proteins: A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Radioimmunodetection: Use of radiolabeled antibodies for diagnostic imaging of neoplasms. Antitumor antibodies are labeled with diverse radionuclides including iodine-131, iodine-123, indium-111, or technetium-99m and injected into the patient. Images are obtained by a scintillation camera.Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY).Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Antibodies, Blocking: Antibodies that inhibit the reaction between ANTIGEN and other antibodies or sensitized T-LYMPHOCYTES (e.g., antibodies of the IMMUNOGLOBULIN G class that compete with IGE antibodies for antigen, thereby blocking an allergic response). Blocking antibodies that bind tumors and prevent destruction of tumor cells by CYTOTOXIC T-LYMPHOCYTES have also been called enhancing antibodies. (Rosen et al., Dictionary of Immunology, 1989)Immunotoxins: 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.Caspase 8: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Fetal Death: Death of the developing young in utero. BIRTH of a dead FETUS is STILLBIRTH.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Lymphocytes: 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.Poly(ADP-ribose) Polymerases: 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.HeLa Cells: 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.Caspase 9: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Cytochromes c: Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.Immunoglobulin Idiotypes: Unique genetically-controlled determinants present on ANTIBODIES whose specificity is limited to a single group of proteins (e.g., another antibody molecule or an individual myeloma protein). The idiotype appears to represent the antigenicity of the antigen-binding site of the antibody and to be genetically codetermined with it. The idiotypic determinants have been precisely located to the IMMUNOGLOBULIN VARIABLE REGION of both immunoglobin polypeptide chains.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.Single-Chain Antibodies: A form of antibodies consisting only of the variable regions of the heavy and light chains (FV FRAGMENTS), connected by a small linker peptide. They are less immunogenic than complete immunoglobulin and thus have potential therapeutic use.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Antibodies, Bispecific: 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.Immunization: Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).Antibody-Dependent Cell Cytotoxicity: 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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Immunoglobulin Fragments: Partial immunoglobulin molecules resulting from selective cleavage by proteolytic enzymes or generated through PROTEIN ENGINEERING techniques.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Immunotherapy: 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.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Spleen: An encapsulated lymphatic organ through which venous blood filters.Immunoglobulin Variable Region: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.bcl-X Protein: A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.Cell Adhesion: Adherence of cells to surfaces or to other cells.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Viral Envelope Proteins: Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Attitude to Death: Conceptual response of the person to the various aspects of death, which are based on individual psychosocial and cultural experience.Immunoglobulin A: Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Hydrogen Peroxide: 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.Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies.Viral Proteins: Proteins found in any species of virus.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Microscopy, Immunoelectron: Microscopy in which the samples are first stained immunocytochemically and then examined using an electron microscope. Immunoelectron microscopy is used extensively in diagnostic virology as part of very sensitive immunoassays.Membrane Potential, Mitochondrial: 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.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Indium Radioisotopes: Unstable isotopes of indium that decay or disintegrate emitting radiation. In atoms with atomic weights 106-112, 113m, 114, and 116-124 are radioactive indium isotopes.Antibodies, Heterophile: Antibodies elicited in a different species from which the antigen originated. These antibodies are directed against a wide variety of interspecies-specific antigens, the best known of which are Forssman, Hanganutziu-Deicher (H-D), and Paul-Bunnell (P-B). Incidence of antibodies to these antigens--i.e., the phenomenon of heterophile antibody response--is useful in the serodiagnosis, pathogenesis, and prognosis of infection and latent infectious states as well as in cancer classification.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Peptide Library: A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Receptors, Death Domain: A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.RNA, Small Interfering: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Apoptosis Inducing Factor: A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.Melanoma: 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)Complement System Proteins: 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).Immunoglobulin Light Chains: Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.Staining and Labeling: The marking of biological material with a dye or other reagent for the purpose of identifying and quantitating components of tissues, cells or their extracts.Clone Cells: 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)Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Cytotoxicity, Immunologic: 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.Annexin A5: A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Oligopeptides: Peptides composed of between two and twelve amino acids.
  • On April 19, 2019 , pembrolizumab was approved for use in combination with the small-molecule tyrosine kinase inhibitor axitinib for the first-line treatment of patients with advanced renal cell carcinoma. (ascopost.com)
  • Pembrolizumab carries warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity. (ascopost.com)
  • In renal cell carcinoma , the recommended dose of pembrolizumab is 200 mg via intravenous infusion over 30 minutes every 3 weeks in combination with 5 mg of oral axitinib twice daily until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months in patients without disease progression. (ascopost.com)
  • Pembrolizumab infusion should be interrupted or slowed for grade 1 or 2 infusion-related reactions and permanently discontinued for grade 3 or 4 reactions. (ascopost.com)
  • 1,2 Pembrolizumab was also granted accelerated approval for treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. (ascopost.com)
  • In addition, relationships between clinical response and PD-L2 status were evaluated in tumor tissues from patients with head and neck squamous cell carcinoma (HNSCC) with recurrent or metastatic disease, treated with pembrolizumab. (aacrjournals.org)
  • Both PD-L1 and PD-L2 positivity significantly predicted clinical response to pembrolizumab on combined tumor, stromal and immune cells, with PD-L2 predictive independent of PD-L1. (aacrjournals.org)
  • Clinical response to pembrolizumab in patients with HNSCC may be related partly to blockade of PD-1/PD-L2 interactions. (aacrjournals.org)
  • Moreover, PD-L2 expression was independently associated with clinical response in pembrolizumab-treated patients, indicating that presence or absence of PD-L2 expression may also play a role in response to PD-1 axis targeted therapies. (aacrjournals.org)
  • Phase II study of maintenance pembrolizumab in patients with extensive-stage small cell lung cancer (SCLC). (bioportfolio.com)
  • To assess the efficacy of maintenance pembrolizumab in extensive-stage small cell lung cancer (SCLC) patients, after treatment with platinum/etoposide. (bioportfolio.com)
  • Pembrolizumab works by binding to PD-1 and blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocyte cells which may affect both tumour cells and healthy cells. (eurekalert.org)
  • Pembrolizumab (MK-3475) is another monoclonal antibody (MAb) therapy designed to directly block the interaction between PD-1 and its ligands, without antibody dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC). (nephronpower.com)
  • We report the structure of the human full-length IgG4 S228P anti-PD1 antibody pembrolizumab, solved to 2.3-Å resolution. (biologicmodels.com)
  • 2013. Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) [ASCO abstract (invivogen.com)
  • In syngeneic mouse models, inhibition of PD-1 activity resulted in decreased tumor growth. (ascopost.com)
  • The researchers also identified a potential way to overcome this problem, showing that inhibition of Fcγ receptors prevented removal of anti-PD-1 and prolonged its effects in vivo. (sciencemag.org)
  • The cytotoxicity analysis indicates that most of the obtained palladium(II) complexes show promising growth inhibition in three human cancer cell lines. (bvsalud.org)
  • TIM-3 is mainly expressed on activated CD8+ T cells and suppresses macrophage activation following PD-1 inhibition. (wikipedia.org)
  • Experiments using PD-L1 transfected DCs and PD-1 expressing transgenic (Tg) CD4+ and CD8+ T cells suggest that CD8+ T cells are more susceptible to inhibition by PD-L1, although this could be dependent on the strength of TCR signaling. (wikipedia.org)
  • IL-10-induced immunosuppression is mediated by the inhibition of DC maturation and T-cell and NK-cell functions [ 10 ]. (hindawi.com)
  • T cell inhibition via this receptor occurs through multiple mechanisms. (biomedcentral.com)
  • This study elucidated the involvement of CB 2 in the in vitro inhibition of RCC cells, and future applications of CB 2 agonists in the prevention and management of RCC are discussed. (biomedcentral.com)
  • The role of proteasome inhibition and immunomodulatory therapy are well established, here we focus on novel agents recently identified as having a role in the treatment of mantle cell lymphoma. (pubmedcentralcanada.ca)
  • Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. (nih.gov)
  • We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1. (nih.gov)
  • These results suggest synergistic associations between PD-1/CTLA-4 and PD-1/CD39 in dampening T-cell activation and function along with suppressing tumor-specific immune responses, suggesting that dual blockade of these molecules could be a more effective strategy for inducing antitumor immune responses in CRC. (frontiersin.org)
  • However, under pathophysiological conditions such as cancer, their suppressive functions promote the growth and progress of disease by hindering antitumor immune responses ( 1 ). (frontiersin.org)
  • Modulation of GITR with agonistic antibodies has been shown to amplify the antitumor immune responses in animal models via multiple mechanisms. (cnbc.com)
  • We hypothesize that concomitant PD-1 blockade and GITR triggering would synergistically improve the effector functions of tumor-infiltrating T cells and increase the antitumor immunity. (biomedcentral.com)
  • In present study, we evaluated the antitumor effects and mechanisms of combined PD-1 blockade and GITR triggering in a clinically highly relevant murine ID8 ovarian cancer model. (biomedcentral.com)
  • Combined anti-PD-1/GITR mAb treatment remarkably inhibited peritoneal ID8 tumor growth with 20% of mice tumor free 90 days after tumor challenge while treatment with either anti-PD-1 or anti-GITR mAb alone exhibited little antitumor effect. (biomedcentral.com)
  • The durable antitumor effect was associated with a memory immune response and conferred by CD4 + cells and CD8 + T cells. (biomedcentral.com)
  • More importantly, combined treatment of anti-PD-1/GITR mAb and chemotherapeutic drugs (cisplatin or paclitaxel) further increased the antitumor efficacy with 80% of mice obtaining tumor-free long-term survival in murine ID8 ovarian cancer and 4 T1 breast cancer models. (biomedcentral.com)
  • Combined anti-PD-1/GITR mAb treatment induces a potent antitumor immunity, which can be further promoted by chemotherapeutic drugs. (biomedcentral.com)
  • Monoclonal antibodies can block cellular interactions that negatively regulate T-cell immune responses, such as CD80/CTLA-4 and PD-1/PD1-L, amplifying preexisting immunity and thereby evoking antitumor immune responses. (pnas.org)
  • Interestingly this drug also inhibits ITK, an essential enzyme in Th2 T cells and by doing so it can shift the balance between Th1 and Th2 T cells and potentially enhance antitumor immune responses. (pnas.org)
  • The enhanced therapeutic activity of PD-L1 blockade by ibrutinib was accompanied by enhanced antitumor T-cell immune responses. (pnas.org)
  • Finally, VISTA overexpression on tumor cells interferes with protective antitumor immunity in vivo in mice. (rupress.org)
  • These antagonist monoclonal antibodies are capable of unleashing dormant or exhausted antitumor immunity, which has led to durable complete and partial responses in a large number of patients. (biomedcentral.com)
  • Within the Tregs, newly synthesized TGF-β1 homodimers form disulfide bonds with the transmembrane protein GARP, which acts to chaperone and orient the cytokine for activation at the cell surface. (scienceboard.net)
  • However, the immunomodulatory effects of anti-angiogenic agents in HCC had yet to be elucidated in a clinical setting. (eurekalert.org)
  • However, PD-L1-negative patients may also respond to PD-1 checkpoint blockade, suggesting that other PD-1 ligands may be relevant to the clinical activity of these therapies. (aacrjournals.org)
  • Therapy targeting both PD-1 ligands may provide clinical benefit in these patients. (aacrjournals.org)
  • Immune checkpoint therapies targeting the programmed cell death protein 1 (PD-1) axis have resulted in groundbreaking improvements in clinical response in multiple human cancers ( 1-9 ). (aacrjournals.org)
  • 3,4) The fact that PD-1 is highly upregulated in tumor-infiltrating lymphocytes, as well as the correlation between PD-L1 expression and clinical outcome of patients in many types of solid cancers, has resulted in some seminal clinical trials. (thefreelibrary.com)
  • 6) The importance of the PD-1/PD-L1 axis in cancer immunity has been demonstrated extensively in both animal models and clinical studies. (thefreelibrary.com)
  • Other medications were not studied in patients with hepatic impairment in clinical trials and therefore recommendations for adjustments are not made (Table 1 ). (cureus.com)
  • Clinical trials are ongoing to verify the efficiency of these antibodies for other cancer types and to evaluate strategies to block other checkpoint molecules. (frontiersin.org)
  • We have published hundreds of Carboplatin And Etoposide Plus LBH589 For Small Cell Lung Cancer news stories on BioPortfolio along with dozens of Carboplatin And Etoposide Plus LBH589 For Small Cell Lung Cancer Clinical Trials and PubMed Articles about Carboplatin And Etoposide Plus LBH589 For Small Cell Lung Cancer for you to read. (bioportfolio.com)
  • In addition to the medical data, news and clinical trials, BioPortfolio also has a large collection of Carboplatin And Etoposide Plus LBH589 For Small Cell Lung Cancer Companies in our database. (bioportfolio.com)
  • A pooled analysis of individual patient data from National Clinical Trials Network clinical trials of concurrent chemoradiotherapy for limited-stage small cell lung cancer in elderly patients versus younger patients. (bioportfolio.com)
  • Monoclonal-antibody-based therapies targeting CTLA-4 and/or PD-1 (checkpoint blockade) have yielded significant clinical benefits-including durable responses--to patients with different malignancies. (nih.gov)
  • In fact, a clinical trial is currently being conducted to evaluate the use of such antibodies for the treatment of advanced solid tumor cancers. (scienceboard.net)
  • MATERIALS AND METHODS Search strategy A systematic search of the published literature was done for clinical trials indexed in MEDLINE (1946-April 2017), EMBASE (1988-April 2017), the Cochrane Database of Systematic Reviews (2005-April 2017) and the Cochrane Central Register of Controlled Trials (from database inception through April 2017) using the search strategy described in Supplementary data 1, Item S1. (deepdyve.com)
  • 2007) PD-1 and PD-1 ligands: from discovery to clinical application. (sinobiological.com)
  • Twenty years ago in Clinical Chemistry , cardiac troponin I (cTnI) 3 autoantibodies to the stable portion of cTnI near the carboxyterminal end of the molecule were first identified as an etiology for false-negative cTnI results ( 1 ). (aaccjnls.org)
  • This issue of Clinical Chemistry contains an article in which the authors have evaluated the impact of such antibodies for the various cardiac troponin fragments and complexes in a series of carefully done studies ( 4 ). (aaccjnls.org)
  • While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. (icr.ac.uk)
  • However, a high number of patients still fail to have a clinical response from anti-PD-1 therapy, and in addition patients experienced, sometimes, serious treatment-related side effects. (biomedcentral.com)
  • Both programs are currently in pre-clinical development and are anticipated to enter the clinic in 2016. (cnbc.com)
  • Osimertinib is in clinical development as an adjuvant treatment for resectable, early stage non-small cell lung cancer (NSCLC). (nihr.ac.uk)
  • Protransduzin™ the highly efficient transduction enhancer increases viral gene transfer in pre-clinical and clinical applications, such as ex vivo gene therapy and CAR-T cell development. (jpt.com)
  • Successful clinical trials using monoclonal antibodies targeting PD-1 signaling have boosted preclinical research, encouraging development of novel therapeutics. (jpt.com)
  • To examine clinical predictors of tumor mutational burden (TMB), to explore the association between TMB and DNA repair mutations, and to analyze TMB as a biomarker for response to immune checkpoint blockade in non-small-cell lung cancer. (cdc.gov)
  • Moreover, the strategy of using natalizumab or similar drugs for T cell-mediated paraneoplastic disorders deserves further investigation with prospective clinical trials. (neurology.org)
  • Also, Opdivo® recently fell short to make its endpoint in a clinical trial as a single agent for frontline non-small cell lung cancer (NSCLC) therapy. (patentdocs.org)
  • CULVER CITY, Calif.--( BUSINESS WIRE )-- NantKwest Inc . ( Nasdaq:NK ), a leading, clinical-stage, natural killer cell based therapeutics company, today announced the launch of a novel triple combination, phase II clinical trial in Merkel cell carcinoma (MCC). (biospace.com)
  • In preclinical and human clinical studies conducted by NantKwest, the combination of haNK cells with a number of different therapeutic antibodies, including avelumab, led to enhanced tumor cell killing when compared to the use of the antibody alone. (biospace.com)
  • Still, fewer than a quarter to half of patients, even in highly selected cohorts, have experienced a clinical benefit while on anti-PD-1 or anti-PD-L1 therapies. (springer.com)
  • Tumor-associated PD-L1 expression has been shown to be a predictive marker for response to anti-PD-1 axis targeted therapies. (aacrjournals.org)
  • n = 175) and had received a median of four prior systemic therapies (range = 1-12). (ascopost.com)
  • TSR-022, Tesaro, Inc.) in combination with anti-PD-1 or anti-PD-L1 therapies are ongoing. (wikipedia.org)
  • Despite all of the recent advancements in RCC diagnosis and treatment, the current therapies are unable to completely eliminate RCC cells, which persist after treatment. (biomedcentral.com)
  • Cancer still accounts for 25% of US deaths despite an enormous investment in novel therapies. (prweb.com)
  • GigaGen is a biopharmaceutical company developing novel antibody and T cell therapies derived from immune repertoires. (prweb.com)
  • The goal of combining these therapies is to synergistically maximize the killing of cancer cells while attempting to spare patients from chemotherapy and its associated adverse side effects. (biospace.com)
  • Despite impressive treatment outcomes in a subset of patients who receive these immune therapies, many patients with NSCLC fail to respond to anti-PD-1/PD-L1 and the identification of a biomarker to select these patients remains highly sought after. (springer.com)
  • This mAb contains a modified Fc region designed to limit antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) [2, (invivogen.com)
  • And the suppression of ROS accumulation and the rescue of cell viability in HeLa cells by N-acetyl-L-cysteine (NAC) suggest the possible link between the increase in ROS generation and cytotoxicity of complex 3e. (bvsalud.org)
  • Cytotoxicity can occur at any stage of the cell cycle, but the cell is most vulnerable to action of these drugs in the G1 and S phase. (medscape.com)
  • The aim of this study is to explore whether the potential docetaxel-resistant mechanism is associated with impaired NK cell cytotoxicity toward CRPC cells. (bvsalud.org)
  • METHODS: By performing MTT assay, we explored the role of docetaxel in regulating NK cells' cytotoxicity. (bvsalud.org)
  • Lack of PD-1 expression was further underlined by the analysis of PD-1 expression from B16-F10-derived 3D cultures and ex vivo tumours. (uni-muenchen.de)
  • We performed in vivo mouse xenotransplantation analyses of CD44s and CD44v cells and found that CD44v cells exhibited relatively increased tumorigenicity. (spandidos-publications.com)
  • Agents required to differentiate monocytes into DCs ex vivo, such as prostaglandin E2 and Toll-like receptor ligands (e.g. (hindawi.com)
  • The anti-tumor properties of cannabinoids have been investigated in many in vitro and in vivo studies. (biomedcentral.com)
  • Because other types of effector T cells also express CD4 and CD25, Tregs have been notoriously difficult to study and differentiate from other T cells. (scienceboard.net)
  • These active TGF-β1 exert short-distance immunosuppressive effects on immune cells including effector T cells. (scienceboard.net)
  • Anti-GITR antibodies target glucocorticoid-induced tumor necrosis factor receptor related protein (GITR), which is regularly expressed on the surface of regulatory T-cells (Tregs) and is expressed on the surface of effector T-cells after their activation. (cnbc.com)
  • At the same time, ligation of GITR on surface of Tregs could abrogate suppressive function of these cells on tumor specific effector T-cells thus further augmenting T-cell immune response. (cnbc.com)
  • It is believed the effects of anti-PD-L1 intervention can be enhanced by utilizing a co-stimulatory antibody, like one targeting GITR, that can turn on tumor specific effector T-cells. (cnbc.com)
  • The treatment of anti-PD-1/GITR mAb increased the frequencies of interferon-γ-producing effector T cells and decreased immunosuppressive regulatory T cells and myeloid-derived suppressor cells, shifting an immunosuppressive tumor milieu to an immunostimulatory state in peritoneal cavity. (biomedcentral.com)
  • Monoclonal anti-CD20 antibody, rituximab, in combination of CHOP chemotherapy (R-CHOP) is widely used with favourable results. (clinicaltrials.gov)
  • This multicenter, single-arm, open-label study is being conducted in patients with metastatic Merkel cell carcinoma (mMCC), a rare and aggressive type of skin tumor,[1], who have previously received one line of chemotherapy. (presseportal.de)
  • As we've said previously, we will continue to build our portfolio to optimize our combination approach to provide the best possible outcomes to patients with B-cell malignancies without the need to use harsh chemotherapy, ideally pushing toward a cure. (cnbc.com)
  • 38% ≥ 65 years), 73% were male, 79% were white and 16% Asian, 19% and 80% of patients had a baseline Karnofsky performance score of 70 to 80 and 90 to 100, and patient distribution by International Metastatic Renal Cell Carcinoma Database Consortium risk categories was 31% favorable, 56% intermediate, and 13% poor. (ascopost.com)
  • and 35% had 1 and 65% had at least 2 prior lines of therapy in the recurrent or metastatic setting. (ascopost.com)
  • It has been approved for the treatment of adults with metastatic renal cell carcinoma. (medscape.com)
  • Treatment of metastatic Merkel cell carcinoma (MCC) in adults and children ≥12 years of age. (medicine.com)
  • PD-1 is a member of the extended CD28/CTLA-4 family of T cell regulators. (wikipedia.org)
  • CD28 is expressed by naive and activated T cells and is critical for optimal T cell activation. (rupress.org)
  • Accordingly, additional CD28 family receptors have been identified. (rupress.org)
  • By outcompeting CD28 for binding to B7.1 and B7.2, CTLA-4 can prevent the co-stimulation necessary to generate and maintain T cell activation. (biomedcentral.com)
  • T cell priming and activation occur when the MHC-peptide complex interacts with the T cell receptor (TCR), followed by the engagement of CD28 to B7.1 (CD80) or B7.2 (CD86) coreceptors. (jci.org)
  • The goals of pharmacotherapy in renal cell carcinoma are to induce remission, reduce morbidity, and prevent complications. (medscape.com)
  • Renal cell carcinoma is an immunogenic tumor, and spontaneous regressions have been documented. (medscape.com)
  • Few options are available for the systemic therapy of renal cell carcinoma (RCC), and no hormonal or chemotherapeutic regimen is accepted as a standard of care to treat this disease. (medscape.com)
  • In this study, we investigated the ECS based on CB 1 and CB 2 receptor gene and protein expression in renal cell carcinoma (RCC) cell lines. (biomedcentral.com)
  • Clearance: In patients with advanced renal cell carcinoma, avelumab clearance was 15% higher in those who tested positive for treatment-emergent anti-drug antibodies (ADA) compared to those who tested negative for treatment-emergent ADA. (medicine.com)
  • First-line treatment of advanced renal cell carcinoma (in combination with axitinib). (medicine.com)
  • 1] ISA Therapeutics B.V., 2333 CH Leiden, The Netherlands Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333ZA Leiden, The Netherlands. (nih.gov)
  • TG Therapeutics is a biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B-cell malignancies and autoimmune diseases. (cnbc.com)
  • These findings and the novel anti-PD-1 antibody will facilitate better understanding of the mechanisms of the molecular recognition of PD-1 receptor by anti-PD-1 mAb and, thereby, enable the development of new therapeutics with an expanded spectrum of efficacy for unmet medical needs. (rcsb.org)
  • Anti-PD-L1 therapeutics bind to PD-L1 on tumor cells. (biopharmconsortium.com)