Leukemia: 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)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.HL-60 Cells: 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)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.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.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.Leukemia, Lymphoid: Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.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.Leukemia, Myeloid, Acute: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.Leukemia, Myeloid: Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.Cell Line, Tumor: A cell line derived from cultured tumor cells.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.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.K562 Cells: An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.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.Arabinofuranosylcytosine Triphosphate: A triphosphate nucleotide analog which is the biologically active form of CYTARABINE. It inhibits nuclear DNA synthesis.Leukemia, Monocytic, Acute: An acute myeloid leukemia in which 80% or more of the leukemic cells are of monocytic lineage including monoblasts, promonocytes, and MONOCYTES.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.Inhibitor of Apoptosis Proteins: A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.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.U937 Cells: A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.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.Gene Expression Regulation, Leukemic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in leukemia.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)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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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.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.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.Leukemia, Experimental: Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.Vinca Alkaloids: A group of indole-indoline dimers which are ALKALOIDS obtained from the VINCA genus of plants. They inhibit polymerization of TUBULIN into MICROTUBULES thus blocking spindle formation and arresting cells in METAPHASE. They are some of the most useful ANTINEOPLASTIC AGENTS.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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.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.Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.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.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.Cytarabine: A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)X-Linked Inhibitor of Apoptosis Protein: An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Teniposide: A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Teniposide 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 cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle.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.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.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.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.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Leukemia-Lymphoma, Adult T-Cell: Aggressive T-Cell malignancy with adult onset, caused by HUMAN T-LYMPHOTROPIC VIRUS 1. It is endemic in Japan, the Caribbean basin, Southeastern United States, Hawaii, and parts of Central and South America and sub-Saharan Africa.Leukemia, Promyelocytic, Acute: An acute myeloid leukemia in which abnormal PROMYELOCYTES predominate. It is frequently associated with DISSEMINATED INTRAVASCULAR COAGULATION.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.CASP8 and FADD-Like Apoptosis Regulating Protein: An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Leukemia, T-Cell: A malignant disease of the T-LYMPHOCYTES in the bone marrow, thymus, and/or blood.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.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.Annexin A5: A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.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.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.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.Precursor Cell Lymphoblastic Leukemia-Lymphoma: A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.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.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.DNA, Neoplasm: DNA present in neoplastic tissue.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.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.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Gallium: A rare, metallic element designated by the symbol, Ga, atomic number 31, and atomic weight 69.72.Down-Regulation: A negative 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.Daunorubicin: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Thionucleosides: Nucleosides in which the base moiety is substituted with one or more sulfur atoms.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.Leukemia, Myelogenous, Chronic, BCR-ABL Positive: Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.Etoposide: 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.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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Tretinoin: An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS.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.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Leukemia, Erythroblastic, Acute: A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.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.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.Drug Screening Assays, Antitumor: 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.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.Mice, Inbred C57BLPhorbols: The parent alcohol of the tumor promoting compounds from CROTON OIL (Croton tiglium).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.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Receptors, Glucocorticoid: Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.TNF-Related Apoptosis-Inducing Ligand: A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Purine-Nucleoside Phosphorylase: An enzyme that catalyzes the reaction between a purine nucleoside and orthophosphate to form a free purine plus ribose-5-phosphate. EC 7: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Receptors, Transferrin: Membrane glycoproteins found in high concentrations on iron-utilizing cells. They specifically bind iron-bearing transferrin, are endocytosed with its ligand and then returned to the cell surface where transferrin without its iron is released.Genes, bcl-2: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.Kinetics: The rate dynamics in chemical or physical systems.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Leukemic Infiltration: A pathologic change in leukemia in which leukemic cells permeate various organs at any stage of the disease. All types of leukemia show various degrees of infiltration, depending upon the type of leukemia. The degree of infiltration may vary from site to site. The liver and spleen are common sites of infiltration, the greatest appearing in myelocytic leukemia, but infiltration is seen also in the granulocytic and lymphocytic types. The kidney is also a common site and of the gastrointestinal system, the stomach and ileum are commonly involved. In lymphocytic leukemia the skin is often infiltrated. The central nervous system too is a common site.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.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.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.Dimethyl Sulfoxide: A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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.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).Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.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).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.Leukocytes: White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.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.Epithelial Cells: 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.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.Myeloid Cell Leukemia Sequence 1 Protein: A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.bcl-Associated Death Protein: A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Cytochrome c Group: A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)Caspase 2: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its caspase recruitment domain with CARD SIGNALING ADAPTOR PROTEINS. Caspase 2 plays a role in APOPTOSIS by cleaving and activating effector pro-caspases. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)Antibodies, Monoclonal: Antibodies produced by a single clone of cells.bcl-2 Homologous Antagonist-Killer Protein: A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Ceramides: Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY 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.BH3 Interacting Domain Death Agonist Protein: A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.Leukemia, Lymphocytic, Chronic, B-Cell: A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.Cysteine Endopeptidases: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.Xenograft Model Antitumor Assays: 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.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)Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.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.Mice, Inbred BALB CProtein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.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.Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages.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.Mice, SCID: 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.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.Neoplastic Stem Cells: Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.Proto-Oncogene Proteins c-myc: Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Molecular Weight: The sum of the weight of all the atoms in a molecule.Fusion Proteins, bcr-abl: Translation products of a fusion gene derived from CHROMOSOMAL TRANSLOCATION of C-ABL GENES to the genetic locus of the breakpoint cluster region gene on chromosome 22. Several different variants of the bcr-abl fusion proteins occur depending upon the precise location of the chromosomal breakpoint. These variants can be associated with distinct subtypes of leukemias such as PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; and NEUTROPHILIC LEUKEMIA, CHRONIC.Leukemia L1210Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Antibiotics, Antineoplastic: Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.Endothelial Cells: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Receptors, TNF-Related Apoptosis-Inducing Ligand: Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.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)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.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Fas-Associated Death Domain Protein: A signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Oxides: 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.Acute Disease: Disease having a short and relatively severe course.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.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.Arsenicals: Inorganic or organic compounds that contain arsenic.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.Culture Media, Serum-Free: CULTURE MEDIA free of serum proteins but including the minimal essential substances required for cell growth. This type of medium avoids the presence of extraneous substances that may affect cell proliferation or unwanted activation of cells.RNA, Neoplasm: RNA present in neoplastic tissue.Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.Apoptotic Protease-Activating Factor 1: A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Caspase 1: A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.PiperazinesTestis: The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.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.Oligonucleotides, Antisense: Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.Blast Crisis: An advanced phase of chronic myelogenous leukemia, characterized by a rapid increase in the proportion of immature white blood cells (blasts) in the blood and bone marrow to greater than 30%.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.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.Cyclin-Dependent Kinase Inhibitor p21: A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.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.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
The growth of these leukemic cells are controlled by either initiating cell differentiation or apoptosis to occur. Cell ... K562 cells were the first human immortalised myelogenous leukemia line to be established. K562 cells are of the erythroleukemia ... Many factors and components play a role in the cell cycle of K562 cells in terms of growth, cell differentiation, and apoptosis ... "Knock-down of CIAPIN1 sensitizes K562 chronic myeloid leukemia cells to Imatinib by regulation of cell cycle and apoptosis- ...
... "miR-34a induces the downregulation of both E2F1 and B-Myb oncogenes in leukemic cells". Clinical Cancer Research. 17 (9): 2712- ... "MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells". PLoS One. 7 (1 ... "MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells". Oncogene. 26 (34): 5017- ... "miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53". Blood. 114 (10): 2181-92. doi: ...
miR-638 has additionally been found to be upregulated in the K562 leukaemic cell line. MicroRNA Lu J, Kwan BC, Lai FM, Tam LS, ... "MiR-181a/b significantly enhances drug sensitivity in chronic lymphocytic leukemia cells via targeting multiple anti-apoptosis ... Yang Y, Wang LL, Li YH, Gao XN, Yu L (2011). "[Expression level of miRNA-663 in different leukemic cell lines and its ... pyrene-Induced Human Cell Transformation". Toxicological Sciences. 125 (2): 382-391. doi:10.1093/toxsci/kfr299. PMC 3355321 . ...
U251 glioblastoma cancer cells, ScaBER urinary bladder cancer cells, and K562 erythroleukemia and HL-60 promyelocyte leukemic ... been shown to inhibit CYP2J2 and to suppress the proliferation and cause the apoptosis of various types of human cancer cell ... Tca-8113 cells, HeLa uterine cervix cell lines, A549 cells, MDA-MB-435 breast cells, and HepG2 cells but they had no ... lung cancer A549 cells and NCL-H446 cells, HepG2 liver cancer cells, LS-174 colon cancer cells, SiHa uterine cervix cancer ...
In many tumor cells, it causes selective apoptosis, sparing healthy cells. Edelfosine can activate the Fas/CD95 cell death ... "The antitumor ether lipid Edelfosine (ET-18-O-CH3) induces apoptosis in H-ras transformed human breast epithelial cells: by ... Edelfosine and other ALPs can be used for purging residual leukemic cells from bone marrow transplants. It is an analog of ... Action of Edelfosine Lacking Toxicity with Protective Effect in Experimental Colitis Sensitivity of K562 and HL-60 Cells to ...
Childhood leukemia is a type of leukemia, usually acute lymphocytic leukemia (ALL), and a type of childhood cancer. The cure rate of childhood leukemia is generally higher than adult leukemia, approaching 90%, although side effects of treatment last into adulthood. The older aggressive treatments of cranial irradiation and anthracyclines (such as doxorubicin) caused increased risk of solid tumors, heart failure, growth retardation, and cognitive defects. Leukemia is a hematological malignancy or a cancer of the blood. It develops in the bone marrow, the soft inner part of bones where new blood cells are made. When a child has leukemia, the bone marrow produces white blood cells that do not mature correctly. Normal healthy cells only reproduce when there is enough space for them. The body will regulate the production of ...
M2 is a subtype of AML (Acute Myeloid Leukemia). It is also known as "Acute Myeloblastic Leukemia with Maturation". Acute myeloid leukemia (AML) is a type of cancer affecting blood cells that eventually develop into non-lymphocyte white blood cells. The disease originates from the bone marrow, the soft inner portion of select bones where blood stem cells develop into either lymphocyte or in this particular condition, myeloid cells. This acute disease prevents bone marrow cells from properly maturing, thus causing an accumulation of immature myeloblast cells in the bone marrow. Acute myeloid leukemia is more lethal than chronic myeloid leukemia, a disease that affects the same myeloid cells, but at a different pace. Many of the immature blast cells in acute myeloid ...
Leukemia cutis is the infiltration of neoplastic leukocytes or their precursors into the skin resulting in clinically identifiable cutaneous lesions. This condition may be contrasted with leukemids, which are skin lesions that occur with leukemia, but which are not related to leukemic cell infiltration. Leukemia cutis can occur in most forms of leukemia, including chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, and prolymphocytic leukemia. Granulocytic sarcoma List of cutaneous conditions James, William Daniel; Berger, Timothy G.; Elston, Dirk M. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. pp. 744-5. ISBN ...
T-cell-prolymphocytic leukemia (T-PLL) is a mature T-cell leukemia with aggressive behavior and predilection for blood, bone marrow, lymph nodes, liver, spleen, and skin involvement. T-PLL is a very rare leukemia, primarily affecting adults over the age of 30. It represents 2% of all small lymphocytic leukemias in adults. Other names include T-cell chronic lymphocytic leukemia, "knobby" type of T-cell leukemia, and T-prolymphocytic leukemia/T-cell lymphocytic leukemia. People affected by T-cell prolymphocytic leukemia typically have systemic disease at presentation, including enlargement of the liver and spleen, widespread enlargement of the lymph nodes, and skin infiltrates. Due to the systemic nature of ...
Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a sub-type of chronic lymphocytic leukemia (CLL). Hairy cell leukemia makes up approximately 2% of all leukemias, with fewer than 2,000 new cases diagnosed annually in North America and Western Europe combined. Hairy cell leukemia was originally described as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s. The disease was formally named leukemic reticuloendotheliosis and its characterization significantly advanced by Bertha Bouroncle and colleagues at The Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966, is derived from the "hairy" ...
Monocytic leukemia is a type of myeloid leukemia characterized by a dominance of monocytes in the marrow. When the monocytic cells are predominantly monoblasts, it can be subclassified into acute monoblastic leukemia. Monocytic leukemia is almost always broken down into "acute" and "chronic": acute monocytic leukemia chronic myelomonocytic ...
Natural killer (NK) cell therapy is used in pediatrics for children with relapsed lymphoid leukemia. These patients normally have a resistance to chemotherapy, therefore, in order to continue on, must receive some kind of therapy. In some cases, NK cell therapy is a choice.[8] NK cells are known for their ability to eradicate tumor cells without any prior sensitization to them.[9] One problem when using NK cells in order to fight off lymphoid leukemia is the fact that it is hard to amount enough of them to be effective.[9] One can receive donations of NK cells from parents or relatives through bone marrow transplants. There are also the issues of cost, purity and safety.[10] Unfortunately, there is always the possibility of Graft vs host ...
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cells. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated. Risk factors include smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene. The underlying mechanism involves replacement of normal bone marrow with leukemia cells, which results in a drop in red blood cells, platelets, and normal white blood ...
Most research on MRD has been done on leukaemia, particularly two types: adult chronic myeloid leukemia, and childhood acute lymphoblastic leukemia (the most common childhood cancer). Leukemia is a cancer of cells in the blood, and primarily affects the bone marrow where they are made. For most human leukemias, the cause is not known. Risk factors can include chemicals and X-rays. Leukemia involves a genetic abnormality that can begin in a single cell and then multiply rapidly, leading to a disruption in the proportion of cell types in the blood. When a bone marrow sample is drawn, leukemic cells can be viewed under a microscope. Leukemic cells look like normal immature ...
Acute basophilic leukemia is a rare form of acute myeloid leukemia where blasts are accompanied by abnormal basophils in all stages of differentiation. It would most likely be classified as M0 without electron microscopic confirmation of basophil lineage. Differentiated (basophilic granules by light microscopy) and poorly differentiated cases ; Majority are poorly differentiated. MPO negative by light microscopy; granules positive in a speckled pattern by electron microscopy. Myeloid antigens are expressed. Diagnosis of poorly differentiated cases made by electron microscopy. May manifest basophil and mast cell granules by EM. Cytogenetically heterogeneous but frequently associated with Philadelphia chromosome. There is no clinically distinguishing features but may be more common in children and young adults and carry a poor prognosis. Liu, P.P.; A. Hajara; C. Wijmengac; F.S. Collins (1995). "Molecular pathogenesis of ...
ଫ୍ଲୁଡାରାବିନ (ଇଂରାଜୀ ଭାଷାରେ Fludarabine, ବିକ୍ରୟ ନାମ ଫ୍ଲୁଡାରା) ଏକ କେମୋଥେରାପି ଔଷଧ ଯାହା ଲିଉକେମିଆ ଓ ଲିମ୍ଫୋମା ରୋଗମାନଙ୍କ ଚିକିତ୍ସାରେ ଦିଆଯାଏ । ଏହି ରୋଗ ମାନଙ୍କ ମଧ୍ୟରେ କ୍ରନିକ ଲିମ୍ଫୋସାଇଟିକ ଲିଉକେମିଆ (chronic lymphocytic leukemia), ନନ୍-ହଜକିନସ ଲିମ୍ଫୋମା (non-Hodgkin's lymphoma), ଆକ୍ୟୁଟ ମାୟେଲଏଡ ଲିଉକେମିଆ (acute myeloid leukemia) ଓ ଆକ୍ୟୁଟ ଲୋମ୍ଫୋସାଇଟିକ ଲିଉକେମିଆ (acute lymphocytic leukemia) ଇତ୍ୟାଦି ଅନ୍ତର୍ଭୁକ୍ତ । ଏହି ଔଷଧ ଶିରାଭ୍ୟନ୍ତର ଇଞ୍ଜେକସନ ଆକାରରେ ଦିଆଯାଏ ବା ପାଟିରେ ମଧ୍ୟ ...
Leukemia is a peer-reviewed medical journal published by the Nature Publishing Group. It was established in 1987 by Nicole Muller-Bérat Killman and Sven-Aage Killman, and is currently edited by Professors Andreas Hochhaus and Robert Peter Gale. The journal covers research on all aspects of leukemia and has a 2015 impact factor of 12.104. ...
ଲିଉକେମିଆ (ଆମେରିକିୟ ଇଂରାଜୀରେ Leukemia ଓ ଇଂଲିସ ଇଂରାଜୀରେ leukaemia) ଏକ କର୍କଟ ଦଳର ନାମ ଯାହା ଅସ୍ଥିମଜ୍ଜାରେ ଆରମ୍ଭ ହୁଏ ଓ ଏହା ଯୋଗୁ ଶ୍ୱେତ ରକ୍ତ କଣିକା ସଂଖ୍ୟ ବଢ଼ିଯାଏ । [୧] ଏହି ରକ୍ତ କଣିକାଗୁଡ଼ିକ ସମ୍ପୁର୍ଣ୍ଣଭାବେ ତିଆରି ହୋଇ ନ ଥାଆନ୍ତି, ତେଣୁ ଏମାନଙ୍କର ନାମ ପ୍ରିକର୍ସର ଜୀବକୋଷ ବା ବ୍ଲାଷ୍ଟ ଜୀବକୋଷ ବା ଲିଉକେମିଆ ଜୀବକୋଷ ଦିଆଯାଇଥାଏ ।[୨] ରକ୍ତସ୍ରାବ ଅସୁବିଧା, ଥକ୍କାଣ ଓ ଜ୍ୱର ହୁଏ ତ‌ଥା ସଂକ୍ରମଣ ସଂକଟ ଅଧିକ ରହେ । [୨] ସାଧାରଣ ରକ୍ତ କଣିକା ଅଭାବ ...
Imidazoline I1 receptor signaling is associated with pathways that regulate cell viability leading to varied cell-type specific ... Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells. Samo za ... proapoptotic protein Bax thus inducing the perturbation of the mitochondrial pathway and apoptosis in human leukemic K562 cells ... Moreover, rilmenidine renders K562 cells, which are particularly resistant to chemotherapeutic agents, susceptible to the DNA ...
on two human leukemic cancer cell lines (K562 and HL-60) and J774 as normal cells using alamarBlue (resazurin) assay. PI ... and cleavage of PARP protein confirmed the induction of apoptosis with CH,sub,2,/sub,Cl,sub,2,/sub, extract. Taken together, ... g/mL on K562 and HL-60 cells, respectively, whereas the normal cells were not affected significantly by this extract. Sub-G1 ... The CH,sub,2,/sub,Cl,sub,2,/sub, extract of ,i,A. turanica,/i, showed the most antiproliferative effect on cancer cells among ...
Induction of Apoptosis and Antitumor Activity of Eel Skin Mucus, Containing Lactose-Binding Molecules, on Human Leukemic K562 ... Exogenous and Endogeneous Disialosyl Ganglioside GD1b Induces Apoptosis of MCF-7 Human Breast Cancer Cells. ... Exp Cell Res. 2015 Dec 10;339(2):351-9. doi: 10.1016/j.yexcr.2015.09.001. Epub 2015 Sep 8. ...
Leukemic Cell Lines.. The Bcr/Abl+ human leukemia lines K562 and BV173 were chosen for initial studies on the effects of ... Whereas most K562 cells had undergone apoptosis within 48 h, the BV173 cells were more resistant, as measured by staining with ... Treatment with imatinib induces increased Bim expression and Bim dephosphorylation in Ph1+ human leukemic cells. K562 cells (a ... parental K562 cells, Bim knockdown K562 (subclone #18), or Bcl-2 overexpressing cells (H: high level = K562/Flag-bcl-2.puro.H ...
Sources of cell lines. The human cell lines K-562 (CML), THP-1 (acute myeloid leukemia), HEK-293 (human embryonic kidney) were ... Mitochondrial dissociation of HK-II by 3-BP potentiates the DNR-induced apoptosis in K-562 cells. Next, we investigated the ... of leukemic cell lines K-562 and THP-1 and then investigated if 3-BP can sensitize the leukemic cells K-562 to anti-leukemic ... cell lines and compared with the normal PBMCs (peripheral blood mononuclear cells). Both leukemic K-562 and THP-1 cells showed ...
... and in human leukemic K562 cells [104]. Cam did not induce significant mutagenicity in bone marrow cells of pregnant rats [105 ... and Euc induced apoptosis in two human leukemia cell lines and inhibited DNA synthesis in plant cells [107,108]. On the other ... 8-cineole in two human leukemia cell lines, but not in human stomach cancer cell line. Oncol. Rep. 9757760 ... and on two human cell lines: hepatoma HepG2 (ATCC HB-8065) and B lymphoid NC-NC cells (DSMZ ACC120). We also used the modified ...
Sensitization of human K562 leukemic cells to TRAIL-induced apoptosis by inhibiting the DNA-PKcs/Akt-mediated cell survival ... Human T-cell leukemia virus type 1 Tax-deregulated autophagy pathway and c-FLIP expression contribute to resistance against ... A role for c-FLIPL in the regulation of apoptosis, autophagy, and necroptosis in T lymphocytes. Cell Death Differ. 2013;2:188- ... Yang A, Wilson NS, Ashkenazi A. Proapoptotic DR4 and DR5 signaling in cancer cells: toward clinical translation. Curr Opin Cell ...
... and apoptosis. Similar results were observed in Jurkat, HL-60, and K562 leukemic cells and with other HDIs (e.g., SAHA, MS-275 ... Unexpectedly, treatment of cells with SB±LY resulted in a marked reduction in phosphorylation (activation) of p44/42 mitogen- ... Together, these findings indicate that LY promotes SB-mediated apoptosis through an AKT-independent process that involves MEK/ ... Coexposure of U937 cells for 24 h to marginally toxic concentrations of LY294002 (e.g., 30 μM) and sodium butyrate (SB; 1 mM) ...
Inhibition of PI-3 kinase sensitizes human leukemic cells to histone deacetylase inhibitor-mediated apoptosis through p44/42 ... and apoptosis. Similar results were observed in Jurkat, HL-60, and K562 leukemic cells and with other HDIs (e.g., SAHA, MS-275 ... with an early caspase-independent increase in cytochrome c release and accompanied by a substantial decline in leukemic cell ... Moreover, PMA/FP cotreatment significantly increased apoptosis in HL-60 promyelocytic leukemia cells and in U937 cells ...
... as well as one leukemic cell line (K562). Proteins were resolved by Western blotting and probed for expression of total GSK3β ... Cells were processed as in (A). C, shRNA to p53 reduces levels of apoptosis to DW1/2 in human melanoma cells. Mean cell cycle ... D, overexpression of p53 induces apoptosis in p53-mut cells but not p53-WT cells. 1205Lu cells (p53-WT) and WM852 cells (p53- ... Evidence that GSK3β inhibition induces p53 up-regulation and apoptosis in human melanoma cells. A, GSK3β is expressed in human ...
... subunit by small molecule inhibitor NU7026 sensitizes human leukemic K562 cells to benzene metabolite-induced apoptosis. ... Induction of CYP4F3 by benzene metabolites in human white blood cells in vivo, in human promyelocytic leukemic cell lines, and ... Gene expression in benzene-exposed workers by microarray analysis of peripheral mononuclear blood cells: induction and ... CYP4F3 associated with occupational benzene-induced hepatotoxicity and induction of CYP4F3 by benzene metabolites in HL60 cells ...
Increase in the ratio of mitochondrial Bax/Bcl-XL induces Bax activation in human leukemic K562 cell line. Apoptosis. 2004; 9: ... Cells were prepared from neonatal hearts of Smad1TG and seeded at a density of 1×104 cells per 0.1 mL per well.18 Cells were ... 104 cells per 0.1 mL per well. Cells were exposed to H/R. Cell viability was quantified by MTS assay. Values are relative ... The importance of apoptosis in cell death after ischemia and reperfusion has been demonstrated in in vivo rodent models.2,3⇓ In ...
Musashi2 modulates K562 leukemic cell proliferation and apoptosis involving the MAPK pathway. in Experimental cell research ... IscU is a new substrate of MK2 both in Drosophila cells and in human cells ... induced ICAM-1 expression by altering the cytoplasmic localization of HuR in human lung microvascular endothelial cells. ... Human Polyclonal MAPKAP Kinase 2 Primary Antibody for IHC, WB - ABIN6713457 : Hu, Zhang, Gao, Gao, Xu, Lv, Zhang, Zhu, Zhang, ...
Doxorubicin activates FOXO3a to induce the expression of multidrug resistance gene ABCB1 (MDR1) in K562 leukemic cells. Mol ... Ionizing radiation activates expression of FOXO3a, Fas ligand, and Bim, and induces cell apoptosis. Int J Oncol 2006;29:643-8. ... AKT-dependent phosphorylation of FOXO3a (Thr32, Ser253, and Ser315 for human FOXO3) enhances FOXO3a/14-3-3 interaction and ... in K562 doxorubicin-sensitive leukemic cells (38). In chronic myeloid leukemia, inhibition of BCR-ABL by imatinib activates ...
We then tested PCTP on two human leukemic cell lines: Jurkat leukemia T cells and K562 chronic myelogenous leukemia cells ( ... PCTP induced apoptosis only in Kv1.3-expressing Jurkat cells (54), while it was quite ineffective in killing K562 cells, which ... PCTP is specific in inducing cell death by Kv1.3 inhibition. (A) Jurkat T lymphocytes and leukemic K562 cells were treated for ... For cell death assays of non-adherent cells, cells were incubated with the test substances for 24 h, washed in HBSS, and ...
... did not increase the gadd153 mRNA level in K562 and KCL22 cell lines that were more resistant to apoptosis induction by the ... Increased gadd153 Messenger RNA Level Is Associated with Apoptosis in Human Leukemic Cells Treated with Etoposide. Béatrice ... We have investigated the relationships between gadd153 gene expression and apoptosis induction in four human leukemic cell ... Increased gadd153 Messenger RNA Level Is Associated with Apoptosis in Human Leukemic Cells Treated with Etoposide ...
Das Gupta S, Gomes A, Debnath A, Saha A, Gomes A. Apoptosis induction in human leukemic cells by a novel protein Bengalin, ... venom induced antiproliferative and apoptogenic activity against human leukemic cell lines U937 and K562. Leuk Res. 2007;31(6): ... laryngeal carcinoma cell line), MCF7 (human breast cancer cells), NCI-H358 (human lung adenocarcinoma cells) and MRC5 (normal ... Scorpion (Odontobuthus doriae) venom induces apoptosis and inhibits DNA synthesis in human neuroblastoma cells. Mol Cell ...
"HERG1 Currents in Native K562 Leukemic Cells, The Journal of Membrane Biology" on DeepDyve, the largest online rental service ... differentiation and/or apoptosis. K562 cells (a chronic myeloid leukemic human cell line) express both the full-length (herg1a ... HERG1 Currents in Native K562 Leukemic Cells. HERG1 Currents in Native K562 Leukemic Cells Cavarra, María; Mónaco, Silvana; ... HERG1 Currents in Native K562 Leukemic Cells. Cavarra, María; Mónaco, Silvana; Assef, Yanina; Ibarra, Cristina; Kotsias, ...
... chronic myelogenous leukemia cells (K562), and human acute monocytic leukemia cells (THP-1), through apoptosis and/or cell ... cells, as well as various types of leukemic cells including acute promyelocytic leukemia cells (HL-60), ... Antiproliferative effect of Lignosus rhinocerotis, the Tiger Milk Mushroom on HCT 116 human colorectal cancer cells. TOPROCJ. ... 14-3-3 proteins: key regulators of cell division, signalling and apoptosis. Bioessays. 2001;23:936-46 doi:10.1002/bies.1134 ...
We evaluated the anti-cancer activity of these Annonaceae plants against several human cancer cell lines. The apoptosis ... Results showed that this crude extract arrested cell cycle and increased the percentage of cells in the SubG1 phase in some ... which might be capable of inducing cancer cell apoptotic death in a cell-type specific manner. This suggests, by analyzing the ... suggesting that the effect was in a cell-type specific manner. Interestingly, the induction of apoptotic cell death was ...
... subunit by small molecule inhibitor NU7026 sensitizes human leukemic K562 cells to benzene metabolite-induced apoptosis.. You H ... cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage. ... by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells ... Benzene is an established leukotoxin and leukemogen in humans. We have previously reported that exposure of workers to benzene ...
The growth of these leukemic cells are controlled by either initiating cell differentiation or apoptosis to occur. Cell ... K562 cells were the first human immortalised myelogenous leukemia line to be established. K562 cells are of the erythroleukemia ... Many factors and components play a role in the cell cycle of K562 cells in terms of growth, cell differentiation, and apoptosis ... "Knock-down of CIAPIN1 sensitizes K562 chronic myeloid leukemia cells to Imatinib by regulation of cell cycle and apoptosis- ...
We therefore studied the role of cPLA2 in TNF-induced apoptosis in a series of human leukemic cell lines. Our results confirm ... Ca2+/calmodulin and protein kinase C regulation of serotonin transport in human K562 lymphocytes. Cell. Immunol. 172: 269. ... Susceptibility of leukemic cells to TNF killing. TNF-mediated cytotoxicity was determined in a panel of human leukemic cell ... Lanes are as follows from left to right: 1, U937 cells; 2, HL60 cells; 3, KG1a cells; 4, CEM cells; and 5, CEM/VLB100 cells. ...
... we used WNV-infected glioma cells to study WNV-replication and WNV-induced apoptosis in human brain-derived cells. T98G cells ... We found that WNV infection induces cell death in the brain-derived tumour cell line T98G by apoptosis under involvement of ... WNV replication decreased cell viability and induced apoptosis as indicated by the activation of the effector caspase-3, the ... demonstrating that both caspases are involved in WNV-induced apoptosis. Pan-caspase inhibition prevented WNV-induced apoptosis ...
... cell death caused by ascorbate/menadione-induced oxidative stress in K562 human chronic myelogenous leukemic cells. Int J ... Sodium ascorbate inhibits growth via the induction of cell cycle arrest and apoptosis in human malignant melanoma A375.S2 cells ... Ascorbate (vitamin C) induces cell death through the apoptosis-inducing factor in human breast cancer cells. Oncol Rep. 2007;18 ... cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells. Mol Nutr Food Res. ...
  • In an effort to evaluate the potential anticancer effect of different extracts of A. turanica on human cancer cell lines, we have investigated the possible cytotoxic activity of the n -hexane, CH 2 Cl 2 , EtOAc, EtOH, and EtOH/H 2 O (1 : 1) extracts of A. turanica Krasch. (hindawi.com)
  • Experiments with gene-targeted mice have shown that different BH3-only proteins are required for apoptosis initiation in response to distinct developmental cues and cytotoxic stimuli ( 6 ). (pnas.org)
  • Recently, it was established that venom toxins from scorpions induced cytotoxic, antiproliferative and apoptogenic effects on cancer cells. (scielo.br)
  • Therefore, the present study aims to investigate the cytotoxic activity of Androctonus australis hector (Aah) scorpion venom and its toxic fractions (FtoxG-50 and F3) on NCI-H358 human lung cancer cells. (scielo.br)
  • The present findings showed that F3 fraction was more cytotoxic towards NCI-H358 lung cancer cells with an IC 50 of 27.05 ± 0.70 μg/mL than venom alone (396.60 ± 1.33 μg/mL) and its toxic fraction FtoxG-50 (45.86 ± 0.91 μg/mL). (scielo.br)
  • Nevertheless, F3 fraction was not cytotoxic at these concentrations on normal human lung fibroblast MRC-5 cells. (scielo.br)
  • The role of cPLA 2 in the cytotoxic action of TNF was investigated in a panel of human leukemic cell lines. (jimmunol.org)
  • Pretreatment with 4-bromophenacyl bromide, a cPLA 2 inhibitor, rendered U937 and HL60 cell lines resistant to the cytotoxic effect of TNF. (jimmunol.org)
  • In recent years it became evident that high-dose ascorbate in the millimolar range bears selective cytotoxic effects on cancer cells in vitro and in vivo. (springer.com)
  • Cytotoxic synergy was observed independent of the sequence of addition of two drugs to cultured cells. (bvsalud.org)
  • Resveratrol strongly reduced cytotoxic activities of proteasome inhibitors against leukemic cells. (biomedcentral.com)
  • Knockdown of p27 Kip1 using siRNA dramatically attenuated the protective effects of resveratrol on cytotoxic actions of proteasome inhibitors against leukemic cells. (biomedcentral.com)
  • In the current study, we have found that resveratrol dramatically protects leukemic cells from cytotoxic actions of proteasome inhibitors via p27 Kip1 -mediated G1/S cell cycle arrest. (biomedcentral.com)
  • Ether-linked glycerophospholipids (ether lipids, EL) are membrane-interactive drugs selectively cytotoxic toward neoplastic cells compared with normal cells. (elsevier.com)
  • Apoptotic death is induced selectively by ET-18-OMe in HL60 cells, which are sensitive to the drug's cytotoxic action, but not in the resistant K562 cell line. (elsevier.com)
  • In vitro (cell-free and cellular preparations) and animal studies have shown Viscumin (lectin-1 or ML-1) to be cytotoxic to 3T3 cells, lethal to mice, and a potent inhibitor of protein synthesis. (sigmaaldrich.com)
  • The dose- and time-dependent antitumor and cytotoxic effects of L-asparaginases from Erwinia carotovora (ECAR LANS) and Escherichia coli (MEDAC) have been investigated using human leukemic cells and human and animal solid tumor cells. (chemweb.com)
  • In the present study, cytotoxic and apoptogenic properties of hydro-ethanol extract of B. multifidi was investigated on human prostate cancer cell lines (PC3 and DU 145) and human embryonic kidney 293 (HEK293) cells. (ac.ir)
  • B. multifidi had cytotoxic effect on malignant cells and normal HEK293 cells in a dose-dependent manner and significantly decreased the cell viability (IC 50 values were between 199.2 and 302.9 µg/ml). (ac.ir)
  • Cytotoxic activity of secondary metabolites derived from Artemisia annua L. towards cancer cells in comparison to its designated active constituent artemisinin. (ac.ir)
  • AntiGan (E-Congerine-10423) possesses cytotoxic activity in vitro against two (SW982 and SW872) of the four human tumoral lines used in our study. (ebiotec.com)
  • A pilot study on the DNA-protective, cytotoxic, and apoptosis-inducing properties of olive-leaf extracts. (ac.ir)
  • ABCG2 is localized in the apical region in cells and transports many cytotoxic drugs, detoxified metabolites, toxins and carcinogens . (aiocm.org)
  • The purified infected primary T-cell blasts can then be used as targets in either a degranulation or cytotoxic assay with purified NK cells as the effector population 5-7 . (jove.com)
  • Alternatively, NK cell lytic activity can be evaluated in a cytotoxic assay that allows for the determination of the percentage of target cells lysed by release of 51 Cr from within the target cell in the presence of NK cells. (jove.com)
  • Chemotherapy, using cytotoxic drugs to destroy cancer cells, has been the most effective treatment. (cy7-5-azide.com)
  • The results showed that Adriamycin was more cytotoxic in drug-free K562/ADR cells than drug-resistant K562/ADR cells. (cy7-5-azide.com)
  • Because tumor cells, among others, are killed by cytotoxic T lymphocytes (CTL) in an antigen-specific manner, agents that promote CD8+ T-cell activation and impart strong cytolytic and inflammatory properties, as well as antigen specificity, are ideal candidates for enhancing tumor-antigen-specific immunity. (aacrjournals.org)
  • 4-1BB was discovered more than 2 decades ago in screens for receptors on mouse concanavalin A (ConA)-activated helper and cytotoxic T-cell lines ( 2 ). (aacrjournals.org)
  • FOXO3a overexpression has been shown to inhibit tumor growth in vitro and tumor size in vivo in breast cancer cells ( 12 , 13 ). (aacrjournals.org)
  • TNF causes cytotoxicity in certain tumor cell lines in vitro, such as the murine fibroblast cell line L929 and the human leukemic cell lines U937 and HL60 ( 2 , 3 ). (jimmunol.org)
  • In the era of molecular target therapy, whereas Imatinib has shown a cumulative best complete cytogenetic response rate of 82% and an estimated event free survival at 8 years of 85%, several in vitro data have confirmed that Ph+ CD34+ progenitor cells crammed in BM niches are resistant to TKI treatments. (unina.it)
  • Indeed, compared with single agent treatment, exposure of CML cells to the combination of TKI and JAK inhibitor Ruxolitinib significantly decreased viability of CML cells and increased their apoptosis in vitro. (unina.it)
  • Sesamin, a class of phytoestrogen isolated from sesame seed displaying potent anticancer activity in vitro and in vivo .However, the mechanism by which sesamin mediates anticancer effects on leukemic cells are notfully understood. (arjournals.org)
  • Phycocyanin, a natural product purified from Spirulina, effectively inhibits the pancreatic cancer cell proliferation in vitro and xenograft tumor growth in vivo . (nature.com)
  • A series of in vitro toxicity experiments were performed, using different human tumoral lines treated with different concentrations of the E-Congerine-10423® compound. (ebiotec.com)
  • The present investigation attempted to evaluate the potential of anti-cancer Persian Gulf sea cucumber species Holothuria arenicola (H. arenicola) aqueous extract on mice colon carcinoma cells in vitro and in vivo . (ac.ir)
  • To assess the effects of PDCD2 and NCoR1 expression in vitro, two GIST-derived cell lines (GIST-T1 and GIST882) were (co-)transfected with the expression vectors pEGFP-N1-PDCD2 and pcDNA3.1-NCoR1, after which the cells were subjected to CCK-8, PI staining and Annexin V-FITC/PI double staining assays, respectively. (cancerindex.org)
  • Beedholm, R., Clark, B.F. and Rattan, S.I. (2004) Mild heat stress stimulates 20S proteasome and its 11S activator in human fibroblasts undergoing aging in vitro. (springer.com)
  • And its chemical properties are known to muck up cancer cell replication in vitro. (cmlc.ml)
  • and (ii) paving the way to a risk-adapted individualized cellular therapy with immunomodulatory mesenchymal stem cells and with specific drugs for the protection of the endothelium by the help of 3D in vitro disease models. (ucd.ie)
  • CREB knockdown inhibits leukemic cell proliferation in vitro and in vivo , but does not affect long-term hematopoietic reconstitution. (biomedcentral.com)
  • In vitro 4-1BB signaling (left panel) costimulates CD4+ and CD8+ T cells to comparable extents with respect to cytokine production and upregulation of cell survival genes, and prevents their AICD ( 3-5 ). (aacrjournals.org)
  • Extensive experience both preclinically and clinically with diphtheria fusion toxins suggested this protein synthesis-inactivating peptide could efficiently kill malignant cells in vitro and in vivo. (bloodjournal.org)
  • The cell counting kit (CCK)‑8 method was used to detect the antitumor effect of K562 cells in vitro. (nih.gov)
  • The generation depression effects of K562 cells cultured in vitro were detected using CCK‑8 technology, which revealed a dose and time‑dependent association. (nih.gov)
  • Bagnoli M, Canevari S, Mezzanzanica D. Cellular FLICE-inhibitory protein (c-FLIP) signalling: a key regulator of receptor-mediated apoptosis in physiologic context and in cancer. (springer.com)
  • Cellular FLICE-like inhibitory protein (c-FLIP): a novel target for Taxol-induced apoptosis. (springer.com)
  • Golan-Gerstl R, Wallach-Dayan SB, Zisman P, Cardoso WV, Goldstein RH, Breuer R. Cellular FLICE-like inhibitory protein deviates myofibroblast Fas-induced apoptosis toward proliferation during lung fibrosis. (springer.com)
  • Protein was harvested from a panel of human melanoma cell lines (WM35, WM793, 1205Lu, WM983A, and WM983B) as well as one leukemic cell line ( K562 ). (aacrjournals.org)
  • Activation of cell survival pathways such as phosphoinositide-3-kinase/AKT/IKK or RAS/mitogen-activated protein kinase are known to phosphorylate FOXOs at different sites which cause FOXOs nuclear exclusion and degradation, resulting in the suppression of FOXO's transcriptional activity. (aacrjournals.org)
  • The gadd153 gene encodes the nuclear protein CHOP 10 that acts as a negative modulator of CCAAT/enhancer binding protein transcriptional factors and inhibits cell cycle progression. (aacrjournals.org)
  • We have previously reported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to mediate the cellular response to DNA double strand break (DSB) caused by DNA-damaging metabolites. (cdc.gov)
  • There are many different cellular components involved in the cycle of apoptosis such as, BCR/ABL, Bcl-2, Bax protein, and cytochrome C. The tumor suppressor gene p53 is also important in the cell cycle regulation of K562 cells. (wikipedia.org)
  • Immunoblot and reverse-transcriptase PCR demonstrated that cPLA 2 expression was detectable at both transcriptional and translational levels in all leukemic cell lines studied, although CEM and CEM/VLB 100 cells expressed cPLA 2 mRNA and protein at lower levels. (jimmunol.org)
  • Previous studies have shown that the sensitivity of TNF-resistant cell lines to TNF and cPLA 2 activity increased following exposure to the protein synthesis inhibitors cycloheximide (CHI) or actinomycin D ( 21 ). (jimmunol.org)
  • Regulative Function of Extracelluar Regulated Protein Kinases and Telomerase in Apoptosis of Hepatocarcinomatous Cell SMMC- Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology. (jove.com)
  • Interestingly, nuclear antigen H731 (PDCD4) and CLIP-associating protein 2 isoform X25 (CLASP2) showed increased in sesamin treated cells and associated protein-ligand interaction network with allicin, capsaicin, cucurbitacin B, and rapamycin which are known to activate apoptosis in cancer cells .Then, sesamin could be developed as candidate of alternative leukemia treatment in the future. (arjournals.org)
  • The mRNA and protein levels of basic helix-loop-helix (bHLH) transcription factor T-cell acute lymphocytic leukemia protein 1 (TAL1) and B cell translocation gene 1 (BTG1) were both upregulated after 3 days of ATO and Nilotinib treatment. (biomedcentral.com)
  • After that, fresh complete moderate was put into the lifestyle and after 24 h of incubation, cells had been harvested and examined for appearance of Stat5750 and Bcl-xL Ginsenoside Rb1 manufacture protein. (globaltechbiz.com)
  • Human SIRT1 is an enzyme that deacetylates the p53 tumor suppressor protein. (oalib.net)
  • We investigated sensitivity of tumor cells (seeded at different density) to L-asparaginases, as well the effect of L-asparaginases on cell growth rate, protein and DNA synthesis in the presence of various cytostatics. (chemweb.com)
  • Expression of this gene has been shown to be repressed by B-cell CLL/lymphoma 6 (BCL6), a transcriptional repressor required for lymph node germinal center development, suggesting that BCL6 regulates apoptosis by its effects on this protein. (cancerindex.org)
  • Previously, PDCD2 (programmed cell death protein 2) has been identified as a putative tumor suppressor in gastric cancer. (cancerindex.org)
  • Efficacy was associated with superoxide generation, reduced glutathione levels, and reduced mRNA and protein expression of antioxidant effectors in responding cells. (aacrjournals.org)
  • P-glycoprotein (Pgp), multidrug-resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP/ABCG2) is frequently observed in cancer cell lines selected with chemotherapeutic drugs and critical to clinical drug resistance . (aiocm.org)
  • The second major MDR transporter, multidrug-resistance-associated protein (MRP), was first discovered in a doxorubicin-selected lung cancer cell line . (aiocm.org)
  • Interactions between the histone deacetylase (HDAC) inhibitors suberanoylanilide hydroxamic acid (SAHA) and sodium butyrate (SB) and the heat shock protein (Hsp) 90 antagonist 17-allylamino 17-demethoxygeldanamycin (17-AAG) have been examined in Bcr-Abl + human leukemia cells (K562 and LAMA84), including those sensitive and resistant to STI571 (imatinib mesylate). (aspetjournals.org)
  • The BCR/ABL fusion protein with elevated ABL tyrosine kinase activity is crucial for transformation of hematopoietic cell . (exp-oncology.com.ua)
  • Furthermore, FZD treatment resulted in increased stability of tumor suppressor p53 protein in AML cells. (plos.org)
  • The fact that each miRNA may regulate multiple targets implies that a third of the protein-coding genes in humans may be regulated by miRNAs ( 9 ). (aacrjournals.org)
  • It was later shown that miR-15a and miR-16-1 negatively regulate expression of the BCL2 protein at the posttranscriptional level, inducing apoptosis in leukemic cells ( 11 ). (aacrjournals.org)
  • By staining with a fluorochrome conjugated antibody against CD107a, a lysosomal membrane protein that becomes expressed on the NK cell surface when the cytolytic granules fuse to the plasma membrane, we can determine what percentage of NK cells degranulate in response to target cell recognition. (jove.com)
  • This finding is in line with previous studies that have demonstrated high levels of mRNA and protein expression of MDR1 and CD147 in MDR cancer cell lines . (cy7-5-azide.com)
  • Cells were incubated with varying concentrations of recombinant fusion toxin for 48 hours and incorporation of 3 H-leucine (protein synthesis), segmentation of nuclei after DAPI staining (apoptosis), and colony formation in 0.2% agarose (clonogenicity) were measured. (bloodjournal.org)
  • The constitutive tyrosine kinase activity of Bcr/Abl promotes malignant transformation by activating signaling pathways that stimulate uncontrolled cell proliferation, abnormal cell adhesion, and resistance to many apoptotic stimuli, including various anticancer agents ( 1 ). (pnas.org)
  • E. Western blot of CM and β-actin (top) and relative expression of p53 target genes in sorted AML cells transduced with ctrl-shRNA or CM-shRNA (A3, D4) and induced with IR (bottom). (nih.gov)
  • Leukemia is a malignant disease of blood cells which arises due to mutations in growth promoting genes. (scirp.org)
  • Here we show increased expression of MEIS1, MEIS2, and PREP1 genes in leukemia-derived cell lines compared with blood normal cells. (biomedcentral.com)
  • Our results indicate that up-regulation of MEIS1 is important for sustaining proliferation of leukemic cells and that down-regulation of MEIS1 or up-regulation of PREP1 and PBX genes could be implicated in the modulation of the cellular response to chemotherapeutic-induced apoptosis. (biomedcentral.com)
  • in these mice, leukemic tumors that contain a viral integration site at the MEIS1 locus frequently possess an additional co-integration site in some HOX genes [ 12 ], which suggests the required cooperative effect of MEIS and HOX during leukemogenesis. (biomedcentral.com)
  • By combining our expression data from CREB knockdown cells with prior ChIP data on CREB binding we were able to identify a list of putative CREB regulated genes. (biomedcentral.com)
  • Decreased expression of specific histone genes was validated in K562, TF-1, and primary AML cells transduced with CREB shRNA. (biomedcentral.com)
  • We speculate that regulation of histone genes may play an important role by possibly altering the regulation of DNA replication during the cell cycle. (biomedcentral.com)
  • Two genes are synthetically lethal (SL) when defects in both are lethal to a cell but a single defect is non-lethal. (stanford.edu)
  • A significant enrichment for apoptosis genes, including MCL-1 , was found among the mRNAs inversely correlated with miR-29b expression in 45 primary AML samples. (bloodjournal.org)
  • The CH 2 Cl 2 extract of A. turanica showed the most antiproliferative effect on cancer cells among all tested extracts with IC 50 values of 69 and 104 μ g/mL on K562 and HL-60 cells, respectively, whereas the normal cells were not affected significantly by this extract. (hindawi.com)
  • The effect of phenolics on the cell cycle could probably contribute to the augmented antiproliferative activity of NaB. (bvsalud.org)
  • Resveratrol (3,4′,5-trihydroxystilbene) is a naturally derived phytoalexin stilbene isolated from grapes and other plants, playing an important role in human health and is well known for its extensive bioactivities, such as antioxidation, anti-inflammatory, anticancer. (hindawi.com)
  • In the present study, anti-proliferative effects of dietary polyphenolic compounds have been observed and demonstrated the strong anticancer efficacy of curcumin (CMN), an active constituent of dietary spice (turmeric) using human leukemia cancer cell line. (bvsalud.org)
  • It functions as a pump to remove anticancer drugs from cells, thereby leading to drug resistance. (cy7-5-azide.com)
  • Altered adhesive interactions with marrow stroma of haematopoietic progenitor cells in chronic myeloid leukaemia. (springer.com)
  • C. Western blot of Ac-p53, p53, CM, CBFβ, β-actin in Cbfb 56M/+ BM progenitor cells transduced with MIG-Cre and stimulated with IR (3Gy, 6 h). (nih.gov)
  • Bone marrow progenitor cells from CREB transgenic mice had increased proliferative capacity and were hypersensitive to growth factors compared to normal hematopoietic stems cells (HSCs). (biomedcentral.com)
  • Cell killing is a critical pharmacological activity of imatinib to eradicate Bcr/Abl + leukemias. (pnas.org)
  • Studies using RNAi and cells from gene-targeted mice revealed that Bim plays a major role in imatinib-induced apoptosis of Bcr/Abl + leukemic cells and that the combined loss of Bim and Bad abrogates this killing. (pnas.org)
  • These results demonstrate that Bim and Bad account for most, perhaps all, imatinib-induced killing of Bcr/Abl + leukemic cells and suggest previously undescribed drug combination strategies for cancer therapy. (pnas.org)
  • Previous work has shown that overexpression of Bcl-2 or Bcl-xL ( 7 ) and, to a lesser extent, RNAi-mediated reduction in Bim ( 8 , 9 ), inhibits imatinib-induced killing of Bcr/Abl + leukemic cells. (pnas.org)
  • We demonstrate here that imatinib activates not only Bim, but also Bad and Bmf, and we show that Bim plus Bad account for most, perhaps all, imatinib-induced killing of Bcr/Abl + leukemic cells. (pnas.org)
  • One of these drugs is Imatinib, which inhibits BCR/ABL causing growth to cease and apoptosis to begin. (wikipedia.org)
  • Indeed, we demonstrated that Half maximal inhibitory concentration (IC50) value (calculated on cell viability) of Imatinib, Nilotinib and Dasatinib significantly increased when leukemic cells are exposed to HS5 or HCM. (unina.it)
  • Imatinib-resistant K562 cells (K562R) have been described previously. (haematologica.org)
  • The initial human clinical trials with imatinib (trade name Gleevec) achieved results that were unprecedented. (resveratrolnews.com)
  • Understanding the role of apoptosis in cancer will greatly broaden our knowledge of all stages of the disease process and its treatment. (bvsalud.org)