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.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
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.
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.
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.
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.
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.
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.
A cell line derived from cultured tumor cells.
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.
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.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
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.
The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.
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.
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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
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.
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.
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.
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.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
An alkylating agent of value against both hematologic malignancies and solid tumors.
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.
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)
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.
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.
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.
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.
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.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.
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.
Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.)
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.
Established cell cultures that have the potential to propagate indefinitely.
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
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.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
Elements of limited time intervals, contributing to particular results or situations.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
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.
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.
A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).
An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Glycoproteins found on the membrane or surface of cells.
The action of a drug in promoting or enhancing the effectiveness of another drug.
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.
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.
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.
Antibodies obtained from a single clone of cells grown in mice or rats.
Any of a group of malignant tumors of lymphoid tissue that differ from HODGKIN DISEASE, being more heterogeneous with respect to malignant cell lineage, clinical course, prognosis, and therapy. The only common feature among these tumors is the absence of giant REED-STERNBERG CELLS, a characteristic of Hodgkin's disease.
An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.
The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.
Simultaneous resistance to several structurally and functionally distinct drugs.
A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.
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.
A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
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.
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.
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)
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
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.
A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)
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.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
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.
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.
A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.
A malignant solid tumor arising from mesenchymal tissues which normally differentiate to form striated muscle. It can occur in a wide variety of sites. It is divided into four distinct types: pleomorphic, predominantly in male adults; alveolar (RHABDOMYOSARCOMA, ALVEOLAR), mainly in adolescents and young adults; embryonal (RHABDOMYOSARCOMA, EMBRYONAL), predominantly in infants and children; and botryoidal, also in young children. It is one of the most frequently occurring soft tissue sarcomas and the most common in children under 15. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p2186; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, pp1647-9)
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
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.
Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
A 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)
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.
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.
Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.
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.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
A 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.
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).
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.
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.
Therapeutic act or process that initiates a response to a complete or partial remission level.
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.
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.
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.
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.
A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.
An anti-inflammatory 9-fluoro-glucocorticoid.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
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.
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.
A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.
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)
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A 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.
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)
An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.
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.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.
A relatively slow-growing glioma that is derived from oligodendrocytes and tends to occur in the cerebral hemispheres, thalamus, or lateral ventricle. They may present at any age, but are most frequent in the third to fifth decades, with an earlier incidence peak in the first decade. Histologically, these tumors are encapsulated, relatively avascular, and tend to form cysts and microcalcifications. Neoplastic cells tend to have small round nuclei surrounded by unstained nuclei. The tumors may vary from well-differentiated to highly anaplastic forms. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2052; Adams et al., Principles of Neurology, 6th ed, p655)
Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.
An anaplastic, highly malignant, and usually bronchogenic carcinoma composed of small ovoid cells with scanty neoplasm. It is characterized by a dominant, deeply basophilic nucleus, and absent or indistinct nucleoli. (From Stedman, 25th ed; Holland et al., Cancer Medicine, 3d ed, p1286-7)
A calcium channel blocker that is a class IV anti-arrhythmia agent.
An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)
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.
Tumors or cancer of the LUNG.
Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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.
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)
The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.
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.
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.
A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.
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.
A plant genus of the family Apocynaceae. It is the source of VINCA ALKALOIDS, used in leukemia chemotherapy.
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.
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.
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.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
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).
A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (PERIODIC DISEASE).
Quaternary salts derived from tetrazoles. They are used in tests to distinguish between reducing sugars and simple aldehydes, for detection of dehydrogenase in tissues, cells, and bacteria, for determination of corticosteroids, and in color photography. (From Mall's Dictionary of Chemistry, 5th ed, p455)
Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
Proteins prepared by recombinant DNA technology.
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.
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.
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.
Vinblastine derivative with antineoplastic activity against CANCER. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols (ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS).
A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.
Tumors or cancer of the COLON.
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.
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)
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.
The process by which chemical compounds provide protection to cells against harmful agents.
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.
A general term for various neoplastic diseases of the lymphoid tissue.
This line KB is now known to be a subline of the ubiquitous KERATIN-forming tumor cell line HeLa. It was originally thought to be derived from an epidermal carcinoma of the mouth, but was subsequently found, based on isoenzyme analysis, HeLa marker chromosomes, and DNA fingerprinting, to have been established via contamination by HELA CELLS. The cells are positive for keratin by immunoperoxidase staining. KB cells have been reported to contain human papillomavirus18 (HPV-18) sequences.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
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.
Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.
A malignant tumor of the bone which always arises in the medullary tissue, occurring more often in cylindrical bones. The tumor occurs usually before the age of 20, about twice as frequently in males as in females.
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.
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.
A nitrogen mustard alkylating agent used as antineoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed)
An anthracenedione-derived antineoplastic agent.
A lignan (LIGNANS) found in PODOPHYLLIN resin from the roots of PODOPHYLLUM plants. It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives.
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
Inorganic or organic compounds that contain the basic structure RB(OH)2.
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.
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.
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.
A 150-kDa MAP kinase kinase kinase that may play a role in the induction of APOPTOSIS. It has specificity for MAP KINASE KINASE 3; MAP KINASE KINASE 4; and MAP KINASE KINASE 6.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
A malignant kidney tumor, caused by the uncontrolled multiplication of renal stem (blastemal), stromal (STROMAL CELLS), and epithelial (EPITHELIAL CELLS) elements. However, not all three are present in every case. Several genes or chromosomal areas have been associated with Wilms tumor which is usually found in childhood as a firm lump in a child's side or ABDOMEN.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
4-Methyl derivative of LOMUSTINE; (CCNU). An antineoplastic agent which functions as an alkylating agent.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
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.
Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Tumors or cancer of the human BREAST.
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)
Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.
... microtubule dynamics can have the effect of stopping a cell's cell cycle and can lead to programmed cell death or apoptosis. ... Vinorelbine, Nocodazole, vincristine, and colchicine have the opposite effect, blocking the polymerization of tubulin into ... Some cell types, such as plant cells, do not contain well defined MTOCs. In these cells, microtubules are nucleated from ... Most cells only have one centrosome for most of their cell cycle, however, right before mitosis, the centrosome duplicates, and ...
... also known as vincristine: a vinca alkaloid that binds to the protein tubulin, thereby preventing the formation of microtubules ... which has the ability to kill B cells, be they normal or malignant; Etoposide: a topoisomerase inhibitor from the group of ... epipodofyllotoxins; Prednisolone: a glucocorticoid hormone that can cause apoptosis and lysis of both normal and malignant ... Twice a week a full blood count with white blood cell count (WBC) differential is obtained. Dose escalation above the starting ...
Cancer cells can also cause defects in the cellular pathways of apoptosis (programmed cell death). As most chemotherapy drugs ... Keglevich P, Hazai L, Kalaus G, Szántay C (May 2012). "Modifications on the basic skeletons of vinblastine and vincristine". ... One theory as to why these drugs kill cancer cells is that they induce a programmed form of cell death known as apoptosis. As ... This leads to a form of programmed cell death called apoptosis. Alkylating agents will work at any point in the cell cycle and ...
... causes apoptosis), and decreases angiogenesis.[citation needed] Oncovin, more commonly known as vincristine, is a mitotic ... Cyclophosphamide slows or stops cell growth. It targets cells that are rapidly dividing, which include cancer cells that are ... An important hallmark of cancer, Akt is part of the cell survival pathways by inhibiting apoptosis. There is also evidence that ... Tew, John G.; Kosco, Marie H.; Burton, Gregory F.; Szakal, Andras K. (1990). "Follicular Dendritic Cells as Accessory Cells". ...
Type B cells, which undergo growth and become primary spermatocytes. Anticancer drugs such as doxorubicin and vincristine can ... In addition to a DNA repair response, exposure of spermatogonia to doxorubicin can also induce programmed cell death (apoptosis ... These cells are reserve spermatogonial stem cells which do not usually undergo active mitosis. Type A (pale) cells, with pale ... These are the spermatogonial stem cells that undergo active mitosis. These cells divide to produce Type B cells. ...
The cell then undergoes apoptosis. The vincristine molecule inhibits leukocyte production and maturation. A downside, however, ... to Vincristine is that it does not only affect the division of cancer cells. It affects all rapidly dividing cell types, making ... It works by stopping cells from dividing properly. Vincristine was first isolated in 1961. It is on the World Health ... Production of vincristine required one ton of dried periwinkle leaves to produce one ounce of vincristine. Periwinkle was grown ...
This regimen also does not contain vincristine and can be used in patients with neuropathy. In combination with anti-CD20, ... a monoclonal antibody that is able to kill CD20-positive B cells, either normal or malignant; (C)yclophosphamide - an ... a glucocorticoid hormone that has the ability to cause apoptosis and lysis of lymphocytes, either normal or malignant; (B) ...
CerS5 sensitizes cells to the chemotherapeutic drugs doxorubicin and vincristine, but not to cisplatin or carboplatin. A splice ... indicating the importance of CerS5 activity in the apoptosis pathway. CerS5 (TRH4) mRNA is found in all tissues and is strongly ... as were levels of CerS5 mRNA in the leukemia cells, but not in the colon cancer cells. For this reason, CerS5 looks like a ... In the brain, CerS5 mRNA is detected in most cells within the gray and white matter tissues. ...
Granule cells also showed a 6 times increased rate of apoptosis. Behaviorally, the mice expressed motor and neurophysiological ... and vincristine. GRCh38: Ensembl release 89: ENSG00000223802 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000087408 ... 2004). "Defects in cell growth regulation by C18:0-ceramide and longevity assurance gene 1 in human head and neck squamous cell ... Within the cell, CerS1 is located in the endoplasmic reticulum (ER) and golgi apparatus membrane. CerS1 has two isoforms and ...
The cell then undergoes apoptosis.[16] The vincristine molecule inhibits leukocyte production and maturation.[17] A downside, ... however, to Vincristine is that it does not only affect the division of cancer cells. It affects all rapidly dividing cell ... The liposome encapsulation of vincristine enhances the efficacy of the vincristine drug while simultaneously decreasing the ... "Vincristine". International Drug Price Indicator Guide. Retrieved 28 November 2015.. *^ del Pino BM. Chemotherapy-induced ...
... therefore it is a useful tool in determining apoptosis and distinguishing between dead cells and live ones. "Dactinomycin". The ... with vincristine and cyclophosphamide) for treating rhabdomyosarcoma and Ewing's sarcoma. It is also used as a radiosensitizer ... In cell biology, actinomycin D is shown to have the ability to inhibit transcription. Actinomycin D does this by binding DNA at ... January 2000). "Cell kinetic study of normal human bone marrow hematopoiesis and acute leukemia using 7AAD/PY". European ...
Prolonged arrest of cells in mitosis due to nocodazole treatment typically results in cell death by apoptosis. Another standard ... Several drugs including vincristine and colcemid are similar to nocodazole in that they interfere with microtubule ... Nocodazole is frequently used in cell biology laboratories to synchronize the cell division cycle. Cells treated with ... For cell synchronization experiments, nocodazole is usually used at a concentration of 40-100 ng/mL of culture medium for a ...
Those changes affect the cell's normal functions, including cell proliferation, programmed cell death (apoptosis), and DNA ... vincristine-prednisone-nitrogen mustard-procarbazine mixture) and fumes from painting) Rubber production and crystalline silica ... implicated stem cells include club cells and neuroepithelial cells that express club cell secretory protein. Small-cell lung ... non-small-cell lung carcinoma and small-cell lung carcinoma. The three main subtypes of NSCLC are adenocarcinoma, squamous-cell ...
Following this, cell cycle arrest occurs, which induces programmed cell death (apoptosis).[32][41] Also, these drugs can affect ... The original vinca alkaloids are natural products that include vincristine and vinblastine.[44][45][46][47] Following the ... This leads to a form of programmed cell death called apoptosis.[31][33] Alkylating agents will work at any point in the cell ... Cancer cells can also cause defects in the cellular pathways of apoptosis (programmed cell death). As most chemotherapy drugs ...
... which increases the treatments toxicity to cancer cells without being deadly to the patient. Vincristine is a drug isolated ... leading to a mismatching of nucleotides that triggers apoptosis through the cell's DNA repair mechanisms. Prednisone is a ... "Vincristine - FDA prescribing information, side effects and uses". Retrieved 2018-03-10. "Vincristine: Mechanism of ... halting cell division in metaphase. With their chromosomes unable to separate, the cells ultimately die. Methotrexate, or ...
DOUDICAN, N.; RODRIGUEZ, A.; OSMAN, I. Mebendazole Induces Apoptosis via Bcl-2 Inactivation in Chemoresistant Melanoma Cells. ... Faculty of 1000 evaluation for Repurposing mebendazole as a replacement for vincristine for the treatment of brain tumors.. ... Mebendazole inhibits growth of human adrenocortical carcinoma cell lines implanted in nude mice. Cancer Chemotherapy and ... Stimulation of pro-inflammatory responses by mebendazole in human monocytic THP-1 cells through an ERK signaling pathway. ...
... receptors for cell surface collagen, receptors involved in neuronal apoptosis, neuronal crest cell development, and an enzyme ... Of the vinca alkaloids, the most neurotoxic drug is vincristine. Vincristine disrupts the microtubular axonal transport system ... This damage can cause neuronal apoptosis, programmed cell death, which leads to neuropathy. Additionally, functional neuronal ... and non-small cell lung cancer. These drugs inhibit the assembly of microtubules and thus disrupt axonal transport in the cell ...
Rapamycin has shown to induce cancer cell death by stimulating autophagy or apoptosis, but the molecular mechanism of apoptosis ... It enhances antitumor activity of some other drugs such as vincristine. Dactolisib seems to inhibit effectively both wild-type ... A G0-G1 cell-cycle blockage can be the consequence of inactivation of mTOR in hypoxia-activated pericytes and endothelial cells ... might not need high doses of mTOR inhibitors to trigger apoptosis. In most cases, cancer cells might only be partially ...
Monoclonal Antibodies (mAb) utilizes antibodies to target tumours, it induces apoptosis of the tumour through the obstruction ... vincristine, and prednisone are used in combination at a relatively high dosage. However, outcomes of the CHOP regimen are ... Nodal T-cell lymphoma subtypes such as Peripheral T-cell lymphoma will often develop this symptom. T-cell lymphoma can cause ... Stem cell transplants can either be an autologous stem cell transplant (ASCT) in which the patient donates their own stem cells ...
Rapamycin has shown to induce cancer cell death by stimulating autophagy or apoptosis, but the molecular mechanism of apoptosis ... It enhances antitumor activity of some other drugs such as vincristine.[20] Dactolisib seems to inhibit effectively both wild- ... A G0-G1 cell-cycle blockage can be the consequence of inactivation of mTOR in hypoxia-activated pericytes and endothelial cells ... and decreased cell survival.[6] Rapamycin has also shown to induce p53-independent apoptosis in certain types of cancer.[5] ...
MBZ induced a dose- and time-dependent apoptotic response in human lung cancer cell lines, and apoptosis via Bcl-2 inactivation ... April 2017). "Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors". Molecular Medicine. ... Treatment of lung cancer cell lines with MBZ caused mitotic arrest, followed by apoptotic cell death with the feature of ... drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells". Molecular ...
Proliferating cancer cells need to replicate their DNA and undergo programmed cell death (apoptosis) in response to DNA strand ... For Hodgkin's it is often used together with chlormethine, vincristine, and prednisone while for brain cancers such as ... Normal or non-proliferating cells are more apt to repair the DNA damage, but still some of the healthy cells will be damaged. ... Common side effect include low blood cell counts and vomiting. Other side effects include tiredness and depression. It is not ...
"Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell ... when replacing vincristine in the process. Bortezomib was also evaluated together with other drugs for the treatment of ... thereby triggering programmed cell death in neoplastic cells. Recently, it was found that bortezomib caused a rapid and ... In normal cells, the proteasome regulates protein expression and function by degradation of ubiquitylated proteins, and also ...
Vincristine): used to inhibit the growth of cancer cells by stopping one cancer cell from splitting into two cells Prednisone: ... the activity of a cell is inhibited and leads to apoptosis. Physicians may recommend patients to undergo autologous stem cell ... Anaplastic Large Cell Lymphoma (ALCL) is a subtype of mature T-cell lymphoma involving T-cells or natural killer (NK) cells, ... adult T-cell leukaemia/lymphoma, enteropathy-type T-cell lymphoma, nasal NK/T-cell lymphoma, hepatosplenic gamma-delta T-cell ...
... as the un-repaired single and double stranded DNA breaks that they cause can lead to apoptosis and cell death. Because of this ... Commonly, TPT is used in conjunction with a combination of drugs such as cyclophosphamide, doxorubicin, and vincristine. It was ... Normal cells have multiple DNA checkpoints that can initiate the removal of these stabilized complexes, preventing cell death. ... TopII is necessary for cell proliferation and is abundant in cancer cells, which make TopoII inhibitors effective anti-cancer ...
... and the tumor cell undergoes apoptosis. Topoisomerase I is an enzyme that mediates reversible single-strand breaks in DNA ... It is a semi-synthetic camptothecin analogue indicated for Small Cell Lung Cancer and Ovarian Cancer, approved in South Korea ...
Decreased apoptosis of crypt stem cells is associated with colon cancer risk. Reduced expression of IRS-1 in Apc (min/+) ... Increased IRS-1 makes MCF-7 cells susceptible to specific chemotherapeutic agents, such as taxol, etoposide, and vincristine. ... LNCaP prostate cancer cells increase cell adhesion and diminish cell motility via IGF-1 independent mechanism, when IRS-1 is ... Overexpression of PTEN in MCF-7 epithelial breast cancer cells inhibits cell growth by inhibiting MAPK pathway. ERK ...
These effects in turn control plasma cell proliferation, survival, apoptosis, adhesion to bone marrow, genome stability, and ... and dexamethasone or the VCMP regimen of vincristine, carmustine, melphalan, and prednisone alternating with vincristine, ... Secondary plasma cell leukemia (sPCL) results from the comparatively slow development of plasma cell/plasma cell precursor ... 2x109 plasma cells per liter or, alternatively, >20% of nucleated blood cells being plasma cells. More recently, the Group has ...
... cell survival, and block normal cell death (apoptosis). It has been demonstrated that simply blocking mTOR signaling can result ... Etoposide, vincristine, dactinomycin, and cyclophosphamide have also traditionally been given. Newer chemotherapies, such as ... Cancer stem cells (or cancer-initiating cells) are thought to be a small population of cells within the tumor that are directly ... Different immunotherapies can include manipulation of the body's T-cells, NK cells, or Dendritic cells so they are more ...
... the death by apoptosis of the cells they infect while the product of LMP2A may activate the infected cell's PI3K cell signaling ... vincristine, and prednisone or R-EPOCH [rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin (R- ... CD4+ T cells (i..e T helper cells), CD8+ cells (i.e. cytotoxic T cells), NK cells (i.e. natural killer cells). The mechanism by ... NK cells), Gamma delta T cells (γδ T cells), cytotoxic T cells (CTL), helper T cells (Th cells), and follicular B helper T ...
... neurotrophic signaling may trigger apoptosis rather than survival pathways in cells expressing the p75 receptor in the absence ... vincristine and prednisone or rituximab and bendamustine". Leukemia & Lymphoma. 56 (2): 347-52. doi:10.3109/10428194.2014. ... cell-cell signaling. • positive regulation of brain-derived neurotrophic factor receptor signaling pathway. • collateral ... regulation of protein localization to cell surface. • regulation of receptor activity. • activation of phospholipase C activity ...
... which may result in cell cycle arrest, differentiation, and apoptosis.[12] ... Romidepsin, also known as Istodax, is an anticancer agent used in cutaneous T-cell lymphoma (CTCL) and other peripheral T-cell ... Latently infected T-cells were exposed in vitro and ex vivo to romidepsin, leading to an increase in detectable levels of cell- ... The most significant results were found in the treatment of cutaneous T-cell lymphoma (CTCL) and other peripheral T-cell ...
The DNA damage induces cell cycle arrest and cellular apoptosis via the accumulation of cytosolic p53 and subsequent activation ... Chlorambucil alkylates and cross-links DNA during all phases of the cell cycle, inducing DNA damage via three different methods ... Chlorambucil produces its anti-cancer effects by interfering with DNA replication and damaging the DNA in a cell. ... The precise mechanisms by which chlorambucil acts to kill tumor cells are not yet completely understood. ...
... apoptosis).[13] This process occurs over approximately 2 months, with a peak level of cell depletion 4-8 weeks after treatment[ ... cladribine targets B cells more than T cells. Both HCL and B-cell chronic lymphocytic leukaemia are types of B cell blood ... the cells with the highest ratios are B cells, especially germinal centre and naive B cells.[17] This again helps to explain ... which causes it to accumulate in cells and interfere with the cell's ability to process DNA. Cladribine is taken up by cells ...
... they accumulate inside the cell and cause initiation of apoptosis.[34] Apoptosis is also encouraged by the blocking of ... which leads to apoptosis of cancer cells that had previously blocked the apoptotic inducing mechanism, leading to tumour ... Abundant formation of microtubules and the prevention of replication caused by docetaxel leads to apoptosis of tumour cells and ... it is cytotoxic to all dividing cells in the body.[23] This includes tumour cells as well as hair follicles, bone marrow and ...
B cell non-Hodgkin lymphoma COP or CVP Cyclophosphamide, Oncovin (vincristine), prednisone Non-Hodgkin lymphoma in patients ... sa pamamagitan ng nakaprogramang kamatayan ng selula na tinaguriang apoptosis. Kung ang pagkakamaling mga prosesong kontrol ay ... B cell non-Hodgkin lymphoma Stanford V Doxorubicin, mechlorethamine, bleomycin, vinblastine, vincristine, etoposide, prednisone ... "Cell. 126 (3): 477-87. doi:10.1016/j.cell.2006.05.051. PMC 2593932. PMID 16901782.. Unknown parameter ,month=. ignored (tulong) ...
DNA crosslinking also has useful merit in chemotherapy and targeting cancerous cells for apoptosis,[1] as well as in ... Eukaryotic yeast cells are also inactivated by one remaining crosslink, but wild type yeast cells can recover from 120 to 200 ... Even though one or two unrepaired crosslinks are sufficient to inactivate a cell, a wild-type bacterial cell can repair and ... "Molecular Cell. 54 (3): 460-471. doi:10.1016/j.molcel.2014.03.015. PMC 5067070. PMID 24726325.. ...
... idelalisib induces apoptosis and prevents proliferation in cell lines derived from malignant B-cells and in primary tumor cells ... It also inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and the CXCR4 and CXCR5 signaling, ... It is also approved for the treatment of follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic lymphoma ( ... PI3Kδ kinase is expressed in normal and malignant B-cells. By inhibiting it, ...
... which inhibits host cells' p53 protein thereby reducing these cells' apoptosis (i.e. programmed cell death) response to injury ... vincristine, and prednisone) was only 10% whereas a more intensive CHO chemotherapy regimen which included high dose ... which binds RB to increase these cells' proliferation; 3) vFLIP, which inhibits host cell's apoptosis and activates these cells ... induces these cells to produce VEGF, a cytokine that feeds back on these cells to inhibit their apoptosis and to increase the ...
... which are cell signaling proteins that block the infected cells apoptosis responses and stimulates their proliferation). The ... vincristine, and prednisone); Overall survival rates with this regimen have been poor, e.g. ~21% after 5 years. More recently, ... Most of these large cells should be B-cells as identified by their expression of B-cell marker proteins (e.g. CD20, CD79a, PAX5 ... In addition to the neoplastic B-cells, these lesions often contain non-neoplastic white blood cells such as T-cell lymphocytes ...
... and protein synthesis in cell-free systems and intact cells". Cancer Res. 36 (8): 2891-5. PMID 1277199. Archived from the ... vincristine, prednisone) and FAC (5-fluorouracil, adriamycin, cyclophosphamide). Doxil (see below) is used primarily for the ... and p53-mediated apoptosis. Doxorubicin-induced cardiomyopathy typically results in dilated cardiomyopathy, with all four ... As a result, DNA damage response, epigenome and transcriptome are deregulated in doxorubicin-exposed cells. In the 1950s, an ...
... makes sure the DNA is copied correctly and destroys the cell (apoptosis) if the DNA is mutated and cannot be fixed. When p53 ... Parasramka S, Talari G, Rosenfeld M, Guo J, Villano JL (July 2017). "Procarbazine, lomustine and vincristine for recurrent high ... Gliomas are classified by cell type, by grade, and by location. Gliomas are named according to the specific type of cell with ... "Cell Phones and Cancer Risk". National Cancer Institute. Retrieved 29 May 2016. "Cell Phones and Cancer Risk (References)". ...
In consequence, BCL2 overexpresses its product, BCL2 apoptosis regulator (i.e. Bcl2). Bcl2 functions to inhibit programmed cell ... vincristine, prednisone and rituximab) in cases of localized, early-stage disease may be appropriate choices for some of these ... These malignant cells often show features of monocytes or plasma cells. Mantle cell lymphomas show monotonous, medium-sized ... In situ follicular lymphoma is an accumulation of monoclonal B cells (i.e. cells descendent from a single ancestral cell) in ...
... regulates cell survival and apoptosis (i.e. programmed cell death) and the product protein of KMT2a viz., MLL regulates cell ... also termed vincristine), and a corticosteroid (i.e. either prednisone or prednisolone) plus the monoclonal antibody ... in which the malignant cells are a type of T cell lymphocyte termed natural killer cells (NK-cells) and 2) intravascular T-cell ... and T-cells and nearby endothelial cells have defects in the expression of proteins required for the NK/T-cells to pass through ...
... *Authors: *Bowen Zhao ... In addition, the effects of matrine on cell apoptosis, proliferation and cell cycle staging together with its potential ... appeared to trigger apoptosis of these cells and had a tendency to arrest the cell cycle at the G0/G1 phase. Matrine treatment ... Effects of matrine on the proliferation and apoptosis of vincristine‑resistant retinoblastoma cells. Exp Ther Med 20: 2838-2844 ...
... accumulation acted as a survival pathway and blocking this pathway could noticeably increase ergolide cytotoxicity on ALL cell ... ConclusionHere we showed that ergolide could be considered as a potent natural compound against leukemic cells by inducing cell ... cycle arrest followed by dose-dependent cell death. Based on results, Autophagy response in a result of ROS ... lactone induces cell cycle arrest along with ROS-dependent apoptosis and potentiates vincristine cytotoxicity in ALL cell lines ...
... produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of ... indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin ... cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The ... V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells ...
Analysis of Cell Cycle and Apoptosis after Combined Treatments.. To ascertain whether the inhibitory effect on TC-71 cell ... Cell Culture and Growth Assay.. Cells (200,000) of TC-71 and SK-N-MC or 500,000 cells of IOR/LAP-35 were seeded in 6-well ... Most anticancer agents, including doxorubicin and vincristine, kill cancer cells by inhibiting cell cycle and/or inducing ... Effects on apoptosis of TC-71 cells by treatments with doxorubicin (DXR) in combination with anti-IGF-IR αIR3 MAb (A) or ...
... thus inhibiting macrophage cell viability and inducing apoptosis. The cell viability inhibition rate and total apoptosis rate ... Vincristine-loaded platelets coated with anti-CD41 mAbs: a new macrophage targeting proposal for the treatment of immune ... Vincristine-loaded platelets coated with anti-CD41 mAbs: a new macrophage targeting proposal for the treatment of immune ... In this study, a novel drug delivery system of vincristine-loaded platelets coated with anti-CD41 mAbs (CD41-VCR-PLT, CD41-VLP ...
After cells divide, they enter a period of growth (ie, phase G1), followed ... more ... Antineoplastic AgentsCancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. ... Cellular apoptosis (ie, programmed cell death) is another potential mechanism of many antineoplastic agents. ... Vincristine (Vincasar PFS). Vincristine is a chemotherapeutic agent derived from the periwinkle plant. This agent acts by ...
Furthermore, we showed that the fungal vincristine was capable of inducing apoptosis in A431 cells through generation of ... Fungal vincristine from Eutypella spp-CrP14 isolated from Catharanthus roseus induces apoptosis in human squamous carcinoma ... vincristine from Eutypella spp-CrP14 isolated from Catharanthus roseus induces apoptosis in human squamous carcinoma cell line- ... We examined its efficacy of apoptotic induction on A431 cells. The parameters examined included cell cycle distribution, loss ...
Different Types of Cell Cycle- and Apoptosis- Related Gene Expressions Alter in Corticosteroid-, Vincristine-, and Melphalan- ... Different Types of Cell Cycle- and Apoptosis- Related Gene Expressions Alter in Corticosteroid-, Vincristine-, and Melphalan- ... In this study, a genome-wide expression analysis of cell cycle- and apoptosis-related genes in corticosteroid-, vincristine-, ... OBJECTIVE: Deregulation of the cell cycle and apoptosis mechanisms in normal cells causes many problems, including cancer. ...
CCKR signaling map, cell differentiation Involved in the activation cascade of caspases responsible for apoptosis ... cells proliferated in the presence of 6nM vincristine, and cell viability was higher than 70%. Control cells were subjected to ... cells were exposed to growing concentrations of vincristine for 48h. B. Cell viability (□) and vincristine concentration (-) ... 3Results3.1After gradual adaptation, the CCRF-SB cell line grew in the presence of 6nM vincristine. Sudden vincristine ...
Expression patterns of cell cycle and apoptosis-related genes in a multidrug-resistant human colon carcinoma cell line.. Scand ... Drug resistant sublines to paclitaxel (MCF-7/Pac) and vincristine (MCF-7/Vinc) that were developed from sensitive MCF-7 cells ( ... Short hairpin RNA targeting beta-catenin suppresses cell proliferation and induces apoptosis in human gastric carcinoma cells. ... The miR-129-1-3p mimics or inhibitors were transfected into the BGC-823 cell line, and the cell cycle and cell growth was ...
The cell then undergoes apoptosis. The vincristine molecule inhibits leukocyte production and maturation. A downside, however, ... to Vincristine is that it does not only affect the division of cancer cells. It affects all rapidly dividing cell types, making ... It works by stopping cells from dividing properly. Vincristine was first isolated in 1961. It is on the World Health ... Production of vincristine required one ton of dried periwinkle leaves to produce one ounce of vincristine. Periwinkle was grown ...
Cotylenin A and vincristine synergistically inhibited the growth and induced apoptosis in myeloma cells. While other ... Combined treatment with cotylenin A and vincristine significantly inhibited the growth of KMS-26 myeloma cells as xenografts. ... However, our study could not explain how the sensitization to vincristine is related to the effects of cotylenin A on the 14-3- ... Cotylenin A has been shown to inhibit the growth of various cancer cells. Herein, we examined the anti-myeloma effects of ...
A drug sensitizes Ewings sarcoma cells to chemotherapy by inducing mitotic arrest and priming the cells for apoptosis. ... A drug sensitizes Ewings sarcoma cells to chemotherapy by inducing mitotic arrest and priming the cells for apoptosis. ... Inhibition of the oncogenic fusion protein EWS-FLI1 causes G2-M cell cycle arrest and enhanced vincristine sensitivity in ... Inhibition of the oncogenic fusion protein EWS-FLI1 causes G2-M cell cycle arrest and enhanced vincristine sensitivity in ...
HeLa cell viability assays showed that light exposure enhanced liposome cytotoxicity and induction of apoptosis. Furthermore, ... as compared with free vincristine sulfate. Keywords: vincristine sulfate, vincristine sulfate-gold nanoparticle conjugates, ... A model drug, vincristine sulfate, was physically conjugated with gold nanoparticles and verified by UV-visible and fourier ... Antitumor efficacy was evaluated in HeLa cells, both in culture and in implants in vivo in nude mice. ...
Celastrol induces vincristine multidrug resistance oral cancer cell apoptosis by targeting JNK1/2 signaling pathway. ... Cell Stem Cell. 2019 Mar 1. pii: S1934-5909(19)30013-X. doi: 10.1016/j.stem.2019.01.013. [Epub ahead of print] ... Mol Cell Proteomics. 2019 Jan 31. pii: mcp.TIR118.001099. doi: 10.1074/mcp.TIR118.001099. [Epub ahead of print] ... Outcome and prognosis of anaplastic large cell lymphoma in children: a report from the Taiwan Pediatric Oncology Group. ...
Effects of kinesins on responses to docetaxel or vincristine. A, KIFC3 inhibits docetaxel-mediated apoptosis, **, P , 0.005 ... Cells and reagents. MDA MB 231 cells and MDA MB 468 cells, kindly provided by Dr. John Pink (Case Western Reserve University, ... The cells were grown for 2 d and plated in six-well plates. When the cells attained 80% confluency, 300,000 cells were replated ... Cell survival was significantly higher in KIFC3 overexpressing cells compared with vector control cells ( Fig. 4A), showing ...
P-glycoprotein and survivin simultaneously regulate vincristine-induced apoptosis in chronic myeloid leukemia cells. ... The pterocarpanquinone LQB-118 induces apoptosis in acute myeloid leukemia cells of distinct molecular subtypes and targets ... Survivin overexpression correlates with an apoptosis-resistant phenotype in chronic myeloid leukemia cells. ... Doxorubicin induces cell death in breast cancer cells regardless of Survivin and XIAP expression levels. ...
PC-3 cells were treated or left untreated with different concentrations of vincristine (A), VP-16 (B), CDDP (C), or ADR (D). ... Cytotoxic Drugs Sensitize PC-3 Cells to TRAIL-Mediated Apoptosis. Human prostate PC-3 cancer cells were used as a model and ... Drug-mediated sensitization of PC-3 cells to TRAIL-induced apoptosis. PC-3 cells were seeded in 24-well plates and subjected to ... Enhancement of TRAIL/Apo2L-mediated apoptosis by adriamycin through inducing DR4 and DR5 in renal cell carcinoma cells. Int J ...
Lack of apoptosis of Sézary cells in the circulation following oral bexarotene therapy. Brit J Dermatol (2005) 152; 1199-1205 [ ... A phase II study of liposomal doxorubicin, vincristine and dexamethasone in multiple myeloma. Leuk Lymphoma (2005) 46; 945-948 ... Centre for Blood Cell Therapies and Cell Therapies Pty Ltd: Cell Processing for Clinical Trials and Commercial Manufacture Cell ... Stem Cell Factor and high-dose twice-daily filgrastim is an effective strategy for peripheral blood stem cell mobilization in ...
... vincristine 0·1 μmol/l) from 24 h to 72 h. (A) early apoptosis (AV+/PI−); (B) late apoptosis/necrosis (AV+/PI+). The results ... PBMC, peripheral blood mononuclear cell; hMSC, human mesenchymal stem cell; NB-4 cell, a leukaemic cell line. ... Apoptosis of hMSCs induced by chemotherapeutic agents. The induction of apoptosis by the five agents that reduced cell number ... Cells were incubated with each chemotherapeutic agent and cell numbers were measured at day 3. The y-axis shows the cell number ...
... inducing apoptosis and targeting specific cytotoxicity to the cancer cells, are drugs of choice. Keeping this in mind, we ... These include vinblastine, vincristine, the camptothecin derivatives, topotecan and irinotecan, etoposide derived from ... cell lines were procured from the National Center for Cell Sciences, Pune, India. Cell lines were grown and maintained in RPMI- ... cells per mL depending upon mass doubling time of cells) was grown in 96-well tissue culture plate and incubated for 24 hours. ...
That cancer cells nonetheless survive implies that they select for blocks in apoptosis. Identifying cancer-specific apoptotic ... Cancer cells exhibit many abnormal phenotypes that induce apoptotic signaling via the intrinsic, or mitochondrial, pathway. ... vincristine, and adriamycin. ... Lymphoma, B-Cell / pathology * Lymphoma, Large B-Cell, Diffuse ... That cancer cells nonetheless survive implies that they select for blocks in apoptosis. Identifying cancer-specific apoptotic ...
In parallel, DTCM-g treatment mediated a significant increase in apoptosis and arrest at the G1 stage of the cell cycle. ... and cell cycle dynamics. The impact on drug interactions in simultaneous treatments with vincristine, methotrexate and 6- ... on four childhood ALL derived cell lines. Methods: REH, NALM-6, MOLT4 and Jurkat cell lines were treated with varied doses of ... Alternatively, DTCM-g failed to potentiate the cytotoxicity of the commonly used drugs in 3 of the ALL cell lines studied. ...
Next Document: Vincristine induces cell cycle arrest and apoptosis in SH-SY5Y human neuroblastoma cells.. ...
In cases where apoptosis is inhibited, however, prolonged autophagy can lead to cell death. This review provides an overview of ... In addition to the regulation of apoptosis, BCL-2 proteins at the ER also regulate autophagy, a survival pathway that limits ... Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 ... Signaling pathways emanating from the endoplasmic reticulum (ER) are involved in apoptosis initiated by stimuli as diverse as ...
... which effects cell division and eventually leads to apoptosis. Vincristine may also have the ability to inhibit the protein ... Vincristines (Oncovin®, Vincasar PFS®, Vincrex®) anti-cancer properties result from its ability to inhibit cell division ... Unlike some of the other vinca alkaloids, vincristine does not cause severe bone marrow suppression (decreased blood cell ... Vincristine is administered intravenously and is used to treat many different types of cancer. It is frequently used in ...
... and vincristine, vinblastine, paclitaxel, docetaxel, etoposide, teniposide, topotecan, and iridotecan as plant alkaloids, but ... Substituted thieno[3,2-b]pyrazines for inhibiting cancer cell proliferation and inducing cancer cell apoptosis ... cell number curve of each cell line. The percent survival was calculated using the following formula: % survival=Nlive cells( ... reduce toxicity to normal cells, and can show effects on selective apoptosis of cancer cells. ...
... including regulation of the balance between cell proliferation and cell death, as well as the modulation of cell adhesion and ... cell migration. Understanding the mechanisms of the regulation of these events can help us foresee the possible impact of ... During the last 40 years, awareness of the role of ChEs role in regulating non-neuromuscular cell-to-cell interactions has been ... However, in the past decades, there has been increasing interest concerning its role in regulating non-neuromuscular cell-to- ...
... vincristine, 15.3 ± 1.1% → 53.5 ± 2.2%). In Daudi-RR1, DHMEQ induces 4.9 ± 1.6% apoptosis and augments drug efficacy ( ... Percentage apoptosis is represented as percentage of hypodiploid cells accumulated at sub-G0 phase of the cell cycle. ... Apoptosis of malignant human B cells by ligation of CD20 with mAbs. Blood 1998; 91: 1644-52. ... Assessment of Apoptosis. DNA fragmentation assay. Percentage of apoptotic cells was determined by evaluation of propidium ...
... and autophagy inhibitor bafilomycinA1 attenuated the suppressive effects of echinatin on cell viability and apoptosis. ... Echinatin, a compound isolated from the Chinese herb Glycyrrhiza uralensis Fisch, was found to markedly induce apoptosis and ... Confocal fluorescence microscopy data showed that echinatin significantly induced autophagy in ESCC cells, ... antitumor effect in the tumor xenograft model and markedly suppressed cell migration and invasion abilities of ESCC cells in a ...
  • Cancer cells exhibit many abnormal phenotypes that induce apoptotic signaling via the intrinsic, or mitochondrial, pathway. (
  • Echinatin, a compound isolated from the Chinese herb Glycyrrhiza uralensis Fisch , was found to markedly induce apoptosis and inhibit proliferation and colony-formation ability in ESCC. (
  • However, imatinib administered alone at doses close to IC 50 for growth inhibition (10 μ m ) did not induce a significant increase in apoptosis. (
  • Phyllanthusmin derivatives induce apoptosis and reduce tumor burden in high grade serous ovarian cancer by late-stage autophagy inhibition. (
  • Bortezomib may induce tumor cell apoptosis or decreased bcl-2 associated drug resistance. (
  • Previously, our group identified a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds that induce apoptosis in cancer cells derived from both solid tumor types and those from hematological malignancies, suggesting their potential as anticancer agents. (
  • The agents in this class target specific antigens in carcinoma cells and induce cytotoxicity. (
  • ML120B down-regulated p-IκBα protein expression in a concentration dependent manner, caused growth inhibition, increased G0/G1 cells, but did not induce apoptosis. (
  • Small molecule XIAP inhibitors cooperate with TRAIL to induce apoptosis in childhood acute leukemia cells and overcome Bcl-2-mediated resistance. (
  • Dramatic elevation of ROS, exceeding compensatory changes in the level of the endogenous thiol buffers, may result in the sustained activation of signaling pathways and expression of genes that induce apoptosis in affected cells. (
  • Another consequence of aging is the accumulation of so-called senescent cells, normal cells that stop dividing, contribute to tissue aging and secrete substances like cytokines that induce inflammation. (
  • For instance, over-expression of survivin has become proven to induce drug resistance against anti-mitotic compounds by stabilizing microtubule network in vincristine/colchicine-resistant oral cancer cells and downregulation of it restores drug sensitivity to individuals compounds during the same cell line. (
  • While it is actually broadly believed that Hsp90 inhibitors induce cancer cell death by indirect down-regulation of survivin as one among its a number of therapeutic functions, a research demonstrated that 17-AAG remedy slightly enhanced the amount of survivin current from the human DU145 prostate cancer cells. (
  • In conclusion, satureja extract has a potential anti-cancer property against human breast cancer cells and its combination with chemotherapeutic agent vincristine may induce cell death effectively and be a potent modality to treat this type of cancer. (
  • Fragmented DNA further confirmed its capacity to induce apoptosis. (
  • Resveratrol has been shown to induce apoptosis Vang et al. (
  • Paradoxical to the cellular transformation potential of c-Myc is its ability to also induce apoptosis. (
  • Etoposide inhibits topoisomerase II and breaks DNA strands, causing cell proliferation to arrest in the late S or early G2 portion of the cell cycle. (
  • However, they were relatively sensitive to a panel of cytotoxic agents, such as paclitaxel, vincristine, etoposide and cytarabine. (
  • Strikingly, BH3 profiling can also predict sensitivity to conventional chemotherapeutic agents like etoposide, vincristine, and adriamycin. (
  • Using four M-phase specific chemotherapeutic agents, Bcl-XL and Bcl-2 provided similar protection against vincristine and vinblastine whereas Bcl-XL afforded as much as 50% greater cell viability than Bcl-2 against etoposide and teniposide-induced cell death. (
  • And also preliminary data indicate that bortezomib can be safely administered in combination with dose adjusted etoposide, prednisolone, vincristine, cyclophosphamide and doxorubicin (EPOCH) chemotherapy. (
  • 1 Because of various mechanisms of action, chemotherapy is synergistic and is best used in combination with the standard three-drug regimen comprising carboplatin, etoposide, and vincristine. (
  • Pubmed ID: 12223143 To study the changes of telomerase activity and protein expression of phosphorylated (activated) extracellular regulated protein kinases (ERK1 and ERK2) in the course of inhibiting hepatocarcinomatous cell proliferation and inducing cell apoptosis by three kinds of chemotherapy drugs: Harringtonine (HRT), Vincristine (VCR), and Etoposide (Vp16). (
  • This is our little attempt to gather information of phytochemicals having anticancer property such as Etoposide, Curcumin, Vincristine, etc. with postulated mechanism. (
  • This review depicts few phytochemicals having anticancer property such as Etoposide, Curcumin, vincristine, etc. with possible mechanism. (
  • Susan Kane, Ph.D., a professor in City of Hope's Department of Cancer Biology , and David Sadava, Ph.D., a visiting professor from the Claremont Colleges, compared effects of the extract silibinin on two specific cancer cell lines that have shown resistance to three common chemotherapeutics - etoposide, doxorubicin and vincristine. (
  • The respective 50% inhibition of cell growth (IC 50 ) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. (
  • In the presence of 12.50 μg/mL of VCR, the respective IC 50 values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro . (
  • Resistance gained by the cells was confirmed with XTT cytotoxicity assay and microarray analyses were carried out. (
  • HeLa cell viability assays showed that light exposure enhanced liposome cytotoxicity and induction of apoptosis. (
  • Alternatively, DTCM-g failed to potentiate the cytotoxicity of the commonly used drugs in 3 of the ALL cell lines studied. (
  • The clones neither responded to rituximab-mediated growth reduction or complement-dependent cytotoxicity nor underwent apoptosis in response to cross-linked rituximab. (
  • Rituximab exerts significant antitumor activity in vivo ( 1 ) via inhibition of cell proliferation or triggering multiple cell-damaging mechanisms, including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity (CDC), and apoptosis ( 16 , 17 ). (
  • 2,3 Vincristine induces cell cycle-specific cytotoxicity by binding to tubulin during mitosis, resulting in microtubule depolymerization and metaphase arrest and thus apoptosis. (
  • The cytotoxicity of ART on Raji cells and Jurkat cells at a low concentration increased when combined with VCR or Ara-C. Apoptosis in Raji cells and Jurkat cells appeared after exposure to ART. (
  • Cytotoxicity was evaluated by MTT assay, reactive oxygen species (ROS), apoptosis and necrosis by flow cytometry, glutathione (GSH) by HPLC, and Bcl-2, Bax and PARP expression by Western blot. (
  • Cytotoxicity of aphidicolin and its derivatives against neuroblastoma cells in vitro: synergism with doxorubicin and vincristine: M. Michaelis, et al. (
  • As with filgrastim, it acts on hematopoietic cells by binding to specific cell surface receptors, thereby activating and stimulating the production, maturation, migration, and cytotoxicity of neutrophils. (
  • The taxol lesion forms rapidly and stably in transition or mitotic cells, because secondary washes to remove residual drug will decrease cytotoxicity except for cells in these populations. (
  • In this study, we investigated whether inhibition of IKK-2 impacts cell growth or cytotoxicity of selected conventional chemotherapeutic agents in non-Hodgkin's lymphoma. (
  • For the first time, this study demonstrates that perturbation of IKK-2 by ML120B leads to synergistic enhancement of vincristine cytotoxicity in lymphoma. (
  • The compounds with the methoxy (in 4c) and methyl (in 4j) substitution were shown to have significant cytotoxicity, with 4c showing dose-dependent activation and decreased cell viability. (
  • Especially the derivatives 18a-f, which did not activate PPARγ to more than 40% at 10â ¯µM, retrieved the cytotoxicity of imatinib in these cells. (
  • Michał Cichocki Tomasz Stefanski Mariusz Kaczmarek Wanda Baer-Dubowska Received: 27 January 2017 / Accepted: 14 May 2018 The Author(s) 2018 Abstract The aim of this study was to evaluate the MCF12A was observed, whereas no significant dif- cytotoxicity of a series of seven 4 -methylthio-trans- ference was observed in cytotoxicity against A431 and stilbene derivatives against cancer cells: MCF7 and HaCaT. (
  • To describe response and event free survival (EFS) in children with neuroblastoma and other solid tumors receiving ABT-751, assess in vitro cytotoxicity of ABT-751 and evaluate the effect of ABT-751 on tubulin polymerization in peripheral blood mononuclear cells (PBMC) and pediatric tumor cell lines. (
  • The sulforhodamine B (SRB) and ACEA Real-Time Cell Electronic Sensing (RT-CES) assays were used to determine the in vitro cytotoxicity. (
  • Generally these phytochemicals treat cancer by different mechanisms like augmenting apoptosis, cell cycle arrest, targeting to some specific cancer inducing proteins, increasing cytotoxicity etc. (
  • The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. (
  • We found 135 proteins exclusively expressed in the presence of vincristine. (
  • The kinesin motor proteins, found in all cells, attach to microtubules and move along them to transport cellular cargoes. (
  • Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the endoplasmic reticulum is now well established. (
  • In addition to the regulation of apoptosis, BCL-2 proteins at the ER also regulate autophagy, a survival pathway that limits metabolic stress, genomic instability and tumorigenesis. (
  • A CAR is a genetically-engineered receptor made so that immune cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22 proteins. (
  • In the present report, we generated clones of FL5.12 lymphoid cells with similar levels of Bcl-2 and Bcl-XL using the Flag epitope to determine if these survival proteins could provide equivalent protection when challenged with chemotherapy or γ-irradiation. (
  • 8,9 The mechanism by which Bcl-2 and Bcl-XL provide chemotherapy resistance is unknown, but it is thought that these survival proteins act at a common final step in the cell death pathway induced by antitumor agents. (
  • In the present studies, we transfected FL5.12 lymphoid cells with expression constructs that produce Flag-epitope tagged Bcl-2 and Bcl-XL and developed cell clones that express similar levels of these proteins as determined with a Flag-specific antibody. (
  • Oncol Rep. 2020 Jul;44(1):103-114 Authors: Yan X, Yang C, Hu W, Chen T, Wang Q, Pan F, Qiu B, Tang B Abstract Keratins are fibrous structural proteins that serve essential roles in forming the stratum corneum and protect the cells in this layer of skin from damage. (
  • In addition, activation of caspase-3 by caspase-9 can be blocked by inhibitor of apoptosis proteins (IAPs). (
  • Thus, IL-4 protects tumor cells from CD95- and chemotherapy-induced apoptosis through the up-regulation of antiapoptotic proteins such as cFLIP/FLAME-1 and Bcl-x L . These findings may provide useful information for the development of therapeutic strategies aimed at restoring the functionality of apoptotic pathways in tumor cells. (
  • The purpose of this study was to explore an approach to overcome radiation resistance by targeting pro-survival Bcl-2 family proteins in breast cancer cells. (
  • Western blotting was used to assay the expression of MDR1/ABCB1 and BCRP/ABCG2 and the apoptosis-related proteins caspase-3, Bcl-2 and Bax. (
  • Under these pro-oxidant conditions, highly reactive radicals can damage DNA, RNA, proteins, and lipid components, which may lead to cell death. (
  • In this way, GSH compartmentalization within the cell has consequences for the activity of proteins that promote cell survival (see Fig. 1 ). (
  • Heat shock protein 90 is really a molecular chaperone that assists the correct folding and stabilization of many proteins in cells. (
  • Moreover, scientific studies showed that Hsp90 stabilizes different vital oncogenic proteins such as survivin, Akt, Erb-2 and HIF-1 in cancer cells. (
  • Though Hsp90 can be a molecular chaperone that assists the correct folding of many proteins in cells, it doesn't bind to unfolded survivin. (
  • In leukemic cells, a proteomics-based target fishing approach revealed that PS89 affects a whole network of endoplasmic reticulum homeostasis proteins. (
  • Most chemotherapeutic treatments rely on cancer cell death in response to DNA damage, although many genotoxic compounds also activate stress pathways independently of DNA damage, for example by inducing reactive oxygen species or binding to proteins within cells. (
  • In general, the induction of DNA damage by genotoxic agents triggers apoptosis initiated by DNA checkpoint proteins such as ataxia telangiectasia mutated (ATM), ataxia telangiectasia mutated and Rad3-related (ATR), and p53 ( Roos and Kaina, 2006 ). (
  • The apoptosis process can be specifically inhibited by a class of proteins known as inhibitors of apoptosis (IAP). (
  • In this study, we present data that shows differential expression levels of collagen genes and proteins in cisplatin- (CIS), paclitaxel- (PAC), doxorubicin- (DOX), topotecan- (TOP), vincristine- (VIN) and methotrexate- (MTX) resistant ovarian cancer cell lines. (
  • The expression pattern of COL genes provide a preliminary view into the role of these proteins in cytostatic drug resistance of cancer cells. (
  • Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. (
  • 1. Amber E I, Henderson R A, Adeyanju J B, Gyang E 0 1990 Single-drug chemotherapy of canine transmissible venereal tumor with cyclophosphamide, methotrexate, or vincristine. (
  • Therefore, it can be possible to improve the poor outcome of patients with PTCLs by a combination of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) with bortezomib as a first-line therapy. (
  • The growth inhibitory effect of ML120B (M) alone and in combination with cyclophosphamide monohydrate (C), doxorubicin (H) or vincristine (V) was evaluated in vitro using short-term culture assay. (
  • More than half of patients with DLBCL can be cured with combination of Rituximab (R) and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). (
  • Lurbinectedin is currently being studied in the global, randomized, phase III ATLANTIS study with doxorubicin versus investigator's choice of either cyclophosphamide, doxorubicin and vincristine or topotecan (NCT02566993). (
  • The patient was referred to the medical oncology department and chemotherapy consisting of vincristine, cyclophosphamide, and cisplatin was started. (
  • 4570-4574, 1996) have previously shown the existence and the pathogenetic relevance of an autocrine loop, mediated by the insulin-like growth factor-I receptor (IGF-IR), which is crucial for survival and proliferation of ES cells in vitro . (
  • Both αIR3 MAb and suramin treatment significantly increased the antitumor in vitro effects of doxorubicin and vincristine, two drugs with a leader action on ES. (
  • IGF-IR, a membrane-bound heterotetramer receptor with intrinsic tyrosine kinase activity, is emerging as an important factor in the regulation of cell growth in different tumor types, both in vitro and in vivo . (
  • Previously we have reported that Eutypella spp - CrP14 isolated from stem cutting of this plant had shown significant antiproliferative activity when tested in vitro against HeLa cell line. (
  • 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. (
  • It has been shown to exhibit potent tumoricidal activity against a variety of human cancer cell lines in vitro and in vivo with minimal or no toxicity to nonmalignant human cells ( 7 ). (
  • Using an in vitro culture system, the chemosensitivity of hMSCs was determined by XTT (2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenylamino) carbonyl]-2 H -tetrazolium hydroxide) assay in comparison with that of NB-4 cells, a leukaemic cell line, and normal peripheral blood mononuclear cells. (
  • Instead, these effects are due to cell-to cell and cell-matrix interactions, through the affinity of membrane-bound AChE molecules to laminin-1, identified previously as an in vitro AChE ligand and, to a lesser extent, to collagen IV and to AChE itself ( Johnson and Moore, 2007 ). (
  • These novel in vitro results denote that continuous long-term rituximab exposure culminates in RR clones that do not respond to rituximab-mediated effects, have altered cellular signaling dynamics, and exhibit different genetic and phenotypic properties compared with parental cells. (
  • In this study, we examined the effects of echinatin on growth, chemosensitivity, and metastatic potential of ESCC cells in vitro and in vivo. (
  • Additionally, Siva‑1 overexpression increased the migration and invasion of KATO III/VCR cells in vitro. (
  • We analyzed the in vitro impact of KIT blockade by imatinib in Ewing tumor cell lines. (
  • We then analyzed if blockade of KIT loop through imatinib (10 μ m ) was able to increase the antitumor in vitro effect of doxorubicin (DXR) and vincristine (VCR), drugs usually used in Ewing tumor treatment. (
  • Primary patient cells with a high Polo-like kinase 1 protein expression were sensitive to the Polo-like kinase 1-specific inhibitor NMS-P937 in vitro , whereas cells with a low expression and normal bone marrow cells were resistant. (
  • Liposomal vincristine has shown greater antitumor activity in vitro and in animal models compared with conventional vincristine at equivalent (mg/kg) doses, and was more likely to be curative in mouse models using leukemia cell lines. (
  • and to explore the mechanism of ART induced apoptosis of tumor cells in vitro. (
  • ART alone or combined with chemotherapy drugs could inhibit the proliferation of B/T lymphocytic tumor cell lines as well ALL primary cells in vitro, probably through the mechanism of apoptosis, which suggest that ART is likely to be a potential drug in the treatment of leukemia/lymphoma. (
  • Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on microtubules in vitro. (
  • They may also be useful as pharmacolocical tools for use in in vitro or in vivo studies to enhance the understanding of the molecular basis of apoptosis (e.g. the pro-apoptotic versus the anti-apoptotic regulatory signal), as well as the pathogenesis of human lymphoid malignancies. (
  • Antihypertensive drug telmisartan suppresses the proliferation of gastric cancer cells in vitro and in vivo. (
  • Children with T-lineage leukaemia are more resistant to a variety of drugs in vitro than B-cell and acute myeloid leukaemia [ 4 ]. (
  • This thesis examined the effect of combinations of different drugs on toxicity to cancer cells in vitro. (
  • In vitro drug sensitivity assay revealed that suppression of NDRG2 could sensitize Hela cells to cisplatin. (
  • Finally, primary breast cancer cells acquired sensitivity to apoptosis in vitro only in the absence of IL-4. (
  • Several FDA-approved drugs were identified that showed potent cytotoxic activity toward retinoblastoma cell lines in vitro. (
  • ABT-751 is active in vitro against adult human tumor cell lines and in in vivo xenograft models of adult and childhood cancers. (
  • While SKi induced apoptosis, ROMe initiated an autophagic cell death in our in vitro cell models. (
  • The partially purified fungal vincristine had strong cytotoxic activity towards human squamous carcinoma cells - A431 in the MTT assay. (
  • It also augments the cytotoxic effects of drugs on drug-resistant NHL B-cells ( 18 ). (
  • Vincristine liposomal is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. (
  • The cytotoxic activity of Pt(II) complex was tested by SRB and ATP cell viability assays. (
  • Zarnani, A.H. A novel platinum-based compound with preferential cytotoxic activity against a panel of cancer cell lines. (
  • Apoptosis plays a pivotal role in the development and maintenance of a functional immune system by ensuring the timely self-destruction of autoreactive immature and mature lymphocytes as well as any emerging target neoplastic cells by cytotoxic T cells. (
  • also contributed to Bcr-Abl-mediated cytotoxic drug resistance in CML cells. (
  • Traditional antineoplastic therapy is based on the use of chemotherapeutic compounds, which exert a cytotoxic effect on proliferating cells and promote the destruction of sensitive tumors ( 1 ). (
  • Apoptosis is the predominant mechanism by which cancer cells die in response to immune attack or to cytotoxic drugs ( 2 , 3 ). (
  • High-throughput screening (HTS) of 2640 approved drugs and bioactive compounds resulted in the identification of cytotoxic agents with potent activity toward both the Y79 and RB355 human retinoblastoma cell lines. (
  • Combination Index showed moderate synergistic cytotoxic effect in both cells. (
  • Many cytotoxic drugs function selectively to kill cancer cells by the abrogation of proliferative signals, leading to cell death, and numerous reports have demonstrated that ROS are generated following treatment with these drugs. (
  • It is of interest to note that all novel compounds were not cytotoxic neither on non-resistant nor on resistant cells. (
  • Cytotoxic drugs used to prevent the replication of cells. (
  • All increase in the percentage of apoptotic cells and G2/M the compounds that were studied exerted a stronger phase arrest in MCF7 and A431 as a result of treatment cytotoxic effect than trans-resveratrol did. (
  • MCF7 cells with 3,4,5-MTS, whereas trans-resveratrol tended to were the most sensitive to the cytotoxic effect of trans- increase the percentage of cells in S phase, particularly resveratrol analogs with IC in the range of in epithelial breast cells MCF12A and MCF7. (
  • Furthermore, we showed that the fungal vincristine was capable of inducing apoptosis in A431 cells through generation of reactive oxygen species and activation of the intrinsic pathway leading to loss of MMP. (
  • The most represented functional categories were: Toll receptor signaling pathway, Ras Pathway, B and T cell activation, CCKR signaling map, cytokine-mediated signaling pathway, and oxidative phosphorylation. (
  • Our data indicate that both PDCD2 and NCoR1 may act as tumor suppressors in GIST cells through the Smad signaling pathway. (
  • However, our study could not explain how the sensitization to vincristine is related to the effects of cotylenin A on the 14-3-3 signaling pathway and further studies will be needed. (
  • Using a panel of 18 lymphoma cell lines, we show that a strategy we have developed, BH3 profiling, can identify apoptotic defects in cancer cells and separate them into three main classes based on position in the apoptotic pathway. (
  • This also includes Ca 2+ -mediated cross talk between ER and mitochondria during apoptosis, which contributes to the mitochondrial dynamics that support the core mitochondrial apoptosis pathway. (
  • Mechanistically, RNA sequencing coupled with bioinformatics analysis and a series of functional assays revealed that echinatin induced apoptosis and autophagy through inactivation of AKT/mTOR signaling pathway, whereas constitutive activation of AKT significantly abrogated these effects. (
  • In both a defined K-Ras-transformed fibroblast model and in human tumor cell lines with mutationally activated Ras, MCP110 selectively synergizes with other agents targeting the mitogen-activated protein kinase pathway, and with multiple agents (paclitaxel, docetaxel, and vincristine) targeting the microtubule network. (
  • In one approach, a single signaling pathway is "vertically" targeted, with drugs inhibiting multiple steps in a signaling cascade: For example, pretreatment of A549 lung carcinoma cells with the phosphatidylinositol 3-kinase inhibitor PX-866, which strongly potentiates the action of the epidermal growth factor receptor inhibitor Iressa ( 9 ). (
  • In recent years, increasing evidences have indicated that highly patterned vasculogenic mimicry (VM) channels are formed by TNBC cells instead of endothelial cells as an alternative microcirculation pathway, and these channel-forming TNBC cells are highly drug resistant [ 7 , 8 ]. (
  • Knockdown of KRT17 decreases osteosarcoma cell proliferation and the Warburg effect via the AKT/mTOR/HIF1 α pathway. (
  • Taken together, these results suggest that mitotic block may not be a sufficient signal for taxol-induced apoptosis and that the taxol lesion initiates apoptosis via a phosphoregulation pathway possibly involving the p34cdc2 kinase. (
  • These results suggest that WNT5A gene silencing reverses VCR resistance in SKOV3/VCR cells possibly through blocking the PI3K/Akt/GSK3β/β-catenin signaling pathway, and thus down-regulating the protein expression levels of MDR1 and Survivin. (
  • Our results indicate that radiation and ABT-737 exert a synergistic effect on breast cancer cell lines through downregulating Mcl-1 and activating the bak-apoptotic pathway. (
  • Nelfinavir induces cell cycle arrest and apoptosis in tumor cells through inhibition of proteasomal degradation and the PI3K/Akt pathway. (
  • Pharmacologic intervention with the PI3K/Akt pathway induced cell death in MM cell lines and primary tumor samples. (
  • These data suggest an important role of the Akt pathway for malignant growth and survival of MM cells also in vivo. (
  • The results suggest that Semecarpus parvifolia Thw induces apoptosis in HEp-2 cells through a NO dependent pathway. (
  • Various research revealed that Curcumin is effective in different types of cancers by increasing apoptosis and targeting specific gene such as MDM2 oncogene is inhibited through the ETS2 transcription factor by modulation of signaling pathway PI3K/mTOR in breast cancer. (
  • We identified S100A8 as the most overexpressed gene, and the cell cycle pathway as the most promising biomarker and therapeutic target for relapsed childhood B-ALL. (
  • SKi treatment induced an increase in SK1 protein levels in Molt-4 cells, whereas it activated the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) pathway in Jurkat and CEM-R cells as protective mechanisms in a sub-population of T-ALL cells. (
  • The effects of matrine on SO‑Rb50 and SO‑RB50/VCR cell growth and proliferation were evaluated using light microscopy and Cell‑Counting Kit‑8 assay. (
  • Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. (
  • Methods: The anti-proliferative activity of the fungal anticancer compound, vincristine was analyzed by MTT assay against different cancer cell lines. (
  • However, doxorubicin did not enhance the autophagy induced by cotylenin A. A colony-forming assay indicated that the combined treatment with cotylenin A and vincristine more effectively suppressed the formation of large colonies, which have higher self-renewal activity than vincristine alone. (
  • The colony formation assay demonstrated that cell growth and proliferation were significantly promoted by Siva‑1 overexpression. (
  • MTT assay was performed to detect the inhibition of proliferation of Raji, Jurkat, and ALL primary cells. (
  • Cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-5-3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2htetrazolium assay. (
  • An assay was developed to analyse how synergy was affected when cells were exposed to the compounds at different times relative to chemotherapeutic drug pulse exposure. (
  • Cell cloning efficiency was evaluated by Colony-forming assay. (
  • CCK-8 assay was used to detect the cell viability of SKOV3/VCR cells. (
  • The multidrug resistant sensitivities of the FaDu/T cells to cisplatin (DDP), 5-fluorouracil (5-FU), doxorubicin (Dox) and vincristine (VCR) were investigated by methyl-thiazolyl-tetrazolium (MTT) assay. (
  • A CCK8 assay was used to determine the effect of TVA and the Mcl-1 inhibitor S63845 on the proliferation of NPC cells. (
  • The mechanism of action of other classes of antitumor drugs, such as Vinca alkaloids, is more related to the inhibition of microtubule formation in the mitotic spindle, resulting in an arrest of the dividing cells at metaphase ( 3 ). (
  • Unlike some of the other vinca alkaloids, vincristine does not cause severe bone marrow suppression (decreased blood cell counts). (
  • In contrast, inhibition of betaIVb-tubulin in PC cells sensitized to vinca alkaloids (Vincristine, Vinorelbine and Vinblastine), which was accompanied by increased apoptosis and enhanced cell cycle arrest. (
  • Vinca alkaloids cause aberrant ROS-mediated JNK activation, Mcl-1 downregulation, DNA damage, mitochondrial dysfunction, and apoptosis in lung adenocarcinoma cells. (
  • 4 First generation vinca alkaloids (vincristine) are associated with more severe neuropathy than the newer vinca alkaloids (vinorelbine, vinflunine). (
  • These include the taxanes (paclitaxel, docetaxel) and the vinca alkaloids (vincristine, vinblastine). (
  • Background: Catharanthus roseus, a medicinal plant, is known to produce secondary metabolites, vincristine and vinblastine, which are terpenoid indole alkaloids. (
  • The most commonly used substances are vinblastine and vincristine, other compounds are vinorelbine and vinflunine. (
  • In general, 4- chlorochablastine and 4-chlorochacristine caused these effects at concentrations higher than those needed for vinblastine, vincristine, and vinorelbine, but the potency was approximately in the range of vinflunine. (
  • Immunofluorescence study of the action of navelbine, vincristine and vinblastine on mitotic and axonal microtubules. (
  • The effect of Siva‑1 overexpression on anticancer drug resistance was assessed by measuring the 50% inhibitory concentration of KATO III/VCR cells to VCR, 5‑fluorouracil and doxorubicin. (
  • Considering the ROS-mediated apoptosis inducing the effect of Pt(II) complex, it warrants further evaluation as a novel metal-containing anticancer drug candidate. (
  • Apoptosis signaling initiated by death receptors or anticancer drugs proceeds through the generation of caspase- and mitochondria-mediated events that result in ultimate cell demise ( 3 ). (
  • The present study was conducted to investigate the anticancer activity and underlying mechanisms of TVA on human nasopharyngeal carcinoma (NPC) 5-8F and CNE-2 cells. (
  • Vincristine was used to evaluate the synergic effect of extract with an anticancer drug. (
  • Studies on anticancer activity of S. parvifolia is lacking and this study was designed to evaluate the antiproliferative activity and the mode of cell death of S. parvifolia Thw. (
  • 2017). and/or cell cycle arrest, among others in breast cancer Molecular mechanisms of anticancer properties of MCF7 cells (Su et al. (
  • Vincristine shows anticancer property by oncogenic EWS-FLI1 fusion protein inhibition which cause G2-M phase cell cycle arrest & reduce tumor. (
  • Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. (
  • Several different mechanisms account for the taxane resistance observed in human tumors and tumor cell lines, including overexpression of the multidrug transporter P-glycoprotein ( 4 ), altered metabolism of the taxane, decreased sensitivity to death-inducing stimuli ( 5 ), alterations in microtubule dynamics, and altered binding of the taxane to its microtubule target ( 6 , 7 ). (
  • Pretreatment of PC-3 cells and other tumor cell lines with various chemotherapeutic drugs sensitized the cells to TRAIL-induced apoptosis concurrently with up-regulation of DR5 expression and inhibition of YY1 expression and its DNA-binding activity. (
  • KIT expression was detected in 4 of 4 Ewing tumor cell lines and in 49 of 110 patient samples (44.5%) by immunohistochemistry and/or Western blot analysis. (
  • Despite absence of c- kit mutations, constitutive and ligand-inducible phosphorylation of KIT was found in all tumor cell lines, indicating an active receptor. (
  • Inhibition of Ewing tumor cell proliferation by imatinib is mediated through blockade of KIT receptor signaling. (
  • We found that IL-4 treatment significantly reduced CD95 (Fas/APO-1)- and chemotherapeutic drug-induced apoptosis in prostate, breast, and bladder tumor cell lines. (
  • The ABT-751 IC 50 was 0.6-2.6 mcM in neuroblastoma and 0.7-4.6 mcM in other solid tumor cell lines. (
  • Functional analyses indicate that survivin is widely involved in many processes of tumorigenesis, including tumor cell proliferation, progression, angiogenesis, therapeutic resistance, and poor prognosis [ 19 ]. (
  • The rate of doxorubicin efflux and apoptosis were detected by flow cytometry. (
  • The results of flow cytometry revealed that the percentage of apoptotic cells decreased following overexpression of Siva‑1. (
  • Apoptotic cells were detected with annexin V staining and flow cytometry. (
  • The apoptosis was analyzed by flow cytometry. (
  • Cell cycle distribution and the cell apoptosis index were quantified using flow cytometry. (
  • Apoptosis was measured using flow cytometry. (
  • The effect of single or combination treatment on cell viability (CellTiterGlo kit), Combination Index (Chou-Talalay method based on median-drug effect analysis), activation of apoptosis and cell cycle modulation (by flow cytometry using Annexin V and propidium iodide respectively) and the expression of associated markers including survivin (Western immunoblot) were determined. (
  • Vincristine induces cell cycle arrest and apoptosis in SH-SY5Y human neuroblastoma cells. (
  • 2OHOA induces cell cycle arrest and apoptosis in several cancer cell lines, including glioma, leukemia, breast and colon cancer lines. (
  • The cover for issue 25 of Oncotarget features Figure 8, 'BI-D1870 in combination with vincristine increase metaphase arrest and apoptosis synergistically,' by Chae, et al. (
  • However, there was strong synergy in the M/V combination where the vincristine concentration can be lowered by a hundred fold in the combination for comparable G2/M arrest and apoptosis. (
  • These alterations are capable to activate several signal transduction pathways, including those involving ATR, p53, p73, and mitogen-activated protein kinase, and culminate in the activation of apoptosis ( 2 ). (
  • Thus, targeting death receptors and their respective signaling pathways to trigger apoptosis in drug-resistant tumor cells is currently being evaluated for cancer therapy. (
  • Apoptosis is essential for normal development and maintenance of homeostasis, and disruption of apoptotic pathways is associated with multiple disease states, including cancer. (
  • Signaling pathways emanating from the endoplasmic reticulum (ER) are involved in apoptosis initiated by stimuli as diverse as ER stress, oncogene expression, death receptor (DR) ligation and oxidative stress, and the BCL-2 family is almost invariably implicated in the regulation of these pathways. (
  • Rituximab failed to chemosensitize the RR clones, which exhibited constitutive hyperactivation of the nuclear factor-κB and extracellular signal-regulated kinase 1/2 pathways, leading to overexpression of B-cell lymphoma protein 2 (Bcl-2), Bcl-2-related gene (long alternatively spliced variant of Bcl-x gene), and myeloid cell differentiation 1 and higher drug resistance. (
  • Unlike parental cells, rituximab neither inhibited the activity of these pathways nor diminished the expression of resistant factors. (
  • Active Ras promotes tumor growth through its ability to activate multiple downstream effector signaling pathways that promote cell proliferation, survival, migration, and angiogenesis (reviewed in refs. (
  • The biologic efficacy of As2O3 in APL and solid tumor cells has been explained through its actions on anti-proliferation, anti-angiogenesis, and apoptotic signaling pathways. (
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (
  • Akt functions to promote cell survival through two distinct pathways. (
  • Cotreatment with Smac mimetics and demethylating agents induces both apoptotic and necroptotic cell death pathways in acute lymphoblastic leukemia cells. (
  • The final outcome of treatment with genotoxicants will also be determined to a large extent by other oncogenic pathways present in the tumor cells as well as by interactions with the cancer microenvironment. (
  • To address these issues, we made use of a panel of cell lines derived from poorly adhesive, integrin β1 knockout cells that were immortalized using simian virus 40 Large T (inactivation of p53 and Rb pathways). (
  • Dysregulation of apoptosis pathways can lead to a number of diseases, including cancer [ 9 , 10 ]. (
  • In different organisms, two conserved apoptosis signaling pathways (intrinsic and extrinsic) have been identified to trigger the apoptotic process through the activation of caspases [ 9 - 11 ]. (
  • Although several genes and signaling pathways are implicated in G1-S regulation, less is known regarding the mechanisms controlling cell cycle progression through G2 and M phases. (
  • The main side effects of vincristine are chemotherapy-induced peripheral neuropathy, hyponatremia, constipation, and hair loss. (
  • Chemotherapy-induced peripheral neuropathy can be severe, and may be a reason to reduce or avoid using vincristine. (
  • The recovery of cell numbers following exposure to chemotherapeutic agents and chemotherapy-induced apoptosis of hMSCs were evaluated. (
  • These results indicate that Bcl-XL and Bcl-2 confer a differential ability to protect against chemotherapy-induced cell death, which appears to be dependent on the molecular mechanism targeted by the drug rather than its cell-cycle phase specificity. (
  • However, the differential ability of Bcl-XL and Bcl-2 against chemotherapy-induced apoptosis was not universal and appeared to be dependent on the molecular mechanism or cellular target of the drug rather than its cell-cycle phase specificity. (
  • Because a Th2 response against tumors is associated with poor prognosis, we investigated the ability of IL-4 to protect tumor cells from death receptor- and chemotherapy-induced apoptosis. (
  • Analysis of the proliferation rate and of apoptosis revealed that αIR3 MAb and suramin significantly enhanced the G 1 -phase rate induced by doxorubicin, without substantially affecting doxorubicin-G 2 -M-blockage of cell cycle, and significantly increased the induction of apoptosis, which confirmed that the specific blockage of IGF-IR deprives ES cells of an important tool for the prevention of drug-induced apoptosis. (
  • We examined its efficacy of apoptotic induction on A431 cells. (
  • Regimen-A included three drugs (dexamethasone, vincristine and asparaginase) and Regimen-B included four drugs (dexa-methasone, vincristine, asparaginase and daunorubicin ) Remission status was assessed after 1 month of induction chemotherapy by blood complete counts and bone marrow examination. (
  • Induction of apoptosis was measured by annexin-V fluorescein isothiocyanate and the level of active caspase 3 positive cells by intracellular staining and flowcytometry. (
  • Several mechanisms have been identified in mammalian cells for the induction of apoptosis. (
  • Induction of apoptosis in Y79 cells was assessed by immunofluorescence detection of activated caspase-3. (
  • To elucidate molecular mechanisms regulating the development of apoptosis resistance, a panel of 15 BL cell lines was investigated for apoptosis induction upon treatment with microtubule inhibitors taxol, nocodazole and vincristine. (
  • Significant differences were observed in the extent of apoptosis induction among BL cell lines examined. (
  • 4N) and vice versa, displaying an inverse relationship between apoptosis and polyploidy induction. (
  • Dominant negative PLK1 mutant induced apoptosis, however, failed to show synergism in induction of apoptosis in combination with microtubule inhibitors. (
  • Drug selection of RPMI-2650 cells resulted in unstable MDR variants, with no induction of invasiveness. (
  • More importantly, we discovered that the Mcl-1 inhibitor S63845 synergistically sensitized NPC cells to apoptosis induction by TVA. (
  • We elucidate that the strong induction of apoptosis in combination with cytostatics is orchestrated by the PS89 target B-cell receptor-associated protein 31, which transduces apoptosis signals at the endoplasmic reticulum -mitochondria interface. (
  • We found that two different osteosarcoma cell lines, U2OS and Saos-2, have relatively higher expression levels of survivin, and specific knockdown of survivin resulted in a number of effects, such as inhibition of cell proliferation, decreased colony formation rate, cell cycle arrest at G2/M phase, induction of apoptosis, and increased sensitivity to cisplatin. (
  • However, matrine at the half‑maximal inhibitory concentration (IC50) appeared to trigger apoptosis of these cells and had a tendency to arrest the cell cycle at the G0/G1 phase. (
  • A novel paradigm to trigger apoptosis in chronic lymphocytic leukemia. (
  • Effector caspases (caspase-3, -6, and -7) play a role in cleaving protein substrates to trigger apoptosis [ 13 ]. (
  • CONCLUSION: This report shows that different types of chemotherapeutic drugs alter different apoptotic and cell cycle-related gene expressions and, as a result, may cause drug-resistant phenotypes in U-266 multiple myeloma cell lines. (
  • Most antineoplastic drugs kill cells predominantly by triggering their apoptotic program ( 1 ). (
  • Addition of imatinib decreased in 15-20 and 15-36% of the proliferative rate of Ewing tumor cells exposed to DXR and VCR, respectively, and increased in 15 and 30% of the apoptotic rate of Ewing tumor cells exposed to the same drugs. (
  • Transfected MCF-7 cells overexpressing the anti-apoptotic Bcl-2 protein, as well as MCF-7-derived vincristine-resistant cell line (Vcr-R) were resistant to both drugs. (
  • Results: The Pt(II) complex treatment resulted in a decrease in cell viability and increasing levels of apoptotic markers (pyknotic nuclei, annexin-V, caspase 3/7 activity) and a decrease in mitochondrial membrane potential in a dose dependent manner. (
  • Conclusion: These findings suggest an upstream role of ROS production in Pt(II) complex-induced ER stressmediated apoptotic cell death. (
  • Several of the biochemical events that contribute to apoptotic cell death as well as both positive and negative regulators of apoptosis have recently been identified (Whyllie A., et al. (
  • Antiproliferative and apoptotic effects of pterostilbene were examined in combination with L-asparaginase in Jurkat cell line. (
  • Pterostilbene increased antiproliferative and apoptotic effects of L-asparaginase in Jurkat cells. (
  • Both G2/M cells and G0/G1 transition cells synchronously initiated apoptotic DNA fragmentation within 20 h of pulsed taxol treatment, indicating that a sustained mitotic block is not requisite to initiate cell death. (
  • The anti-apoptotic ability increased prominently, as the index of apoptosis decreased. (
  • Activation of caspase-8 and cleavage of B-cell receptor-associated protein 31 stimulate a pro-apoptotic crosstalk including release of calcium from the endoplasmic reticulum and an increase in the levels of reactive oxygen species resulting in amplification of mitochondrial apoptosis. (
  • In addition, concomitant treatment of the MCF-7 cells with SKE and vincristine produced a potent anti-proliferative and pro-apoptotic effect compared to extract or drug alone. (
  • The apoptotic response is strongly enhanced by the c-Src[Y530F] oncogene in cells expressing β1 integrins, whereas such sensitization is reduced when these cells are engineered to express β3 integrins instead. (
  • In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. (
  • More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. (
  • Zhou X, Zhang Y, Li Y, Hao X, Liu X, Wang Y. Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells. (
  • OBJECTIVE: Deregulation of the cell cycle and apoptosis mechanisms in normal cells causes many problems, including cancer. (
  • 2-4 Although much progress has been achieved in the detailed characterization of the molecular processes directly involved in drug tolerance of cancer cells, 5,6 more research is needed to develop effective therapeutic strategies to resensitize chemoresistant cells. (
  • Previously, PDCD2 (programmed cell death protein 2) has been identified as a putative tumor suppressor in gastric cancer. (
  • Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. (
  • This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's disease, neuroblastoma, and small cell lung cancer among others. (
  • A downside, however, to Vincristine is that it does not only affect the division of cancer cells. (
  • Cotylenin A has been shown to inhibit the growth of various cancer cells. (
  • A strong promoter was inserted approximately randomly into the genomes of tumor-derived breast cancer cells, using a novel lentiviral vector. (
  • When KIFC3 or the additional kinesins KIFC1, KIF1A, or KIF5A were overexpressed in the breast cancer cell lines MDA-MB231 and MDA-MB 468, the cells became more resistant to docetaxel. (
  • We used the VBIM method to make the novel discovery that overexpression of the kinesin KIFC3 confers resistance to docetaxel in breast cancer cell lines. (
  • In addition to KIFC3, we find that overexpression of a second COOH-terminal kinesin, KIFC1, or of the NH 2 -terminal kinesins KIF5A and KIF1A, all mediate the resistance of breast cancer cells to docetaxel. (
  • SUMOylation modulates FOXK2-mediated paclitaxel sensitivity in breast cancer cells. (
  • 11a-N-Tosyl-5-deoxi-pterocarpan, LQB-223, a novel compound with potent antineoplastic activity toward breast cancer cells with different phenotypes. (
  • Most of the extracts revealed considerable inhibition of MCF-7 cancer cell line. (
  • Cancer is a class of diseases in which a group of cells display uncontrolled growth, invasion, and someti1mes metastasis. (
  • That cancer cells nonetheless survive implies that they select for blocks in apoptosis. (
  • Vincristine is administered intravenously and is used to treat many different types of cancer. (
  • The novel 4-(aryl)-N-(2-alkoxythieno[3,2-b]pyrazin-3-yl)-piperazin-1-carboxamide derivative compound of the present invention can effectively inhibit the growth of proliferating cells, and thus can be useful in the prevention or treatment of cancer. (
  • 9. A method for inhibiting cancer cell proliferation in a subject, comprising administering to the subject the pharmaceutical composition of claim 8. (
  • Esophageal cancer has two major histologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma 2 , and ESCC is the main histologic subtype with ~90% of cases in Asia-Pacific region including China. (
  • Failure of chemotherapy and radiotherapy leads to tumor recurrence and poor prognosis mainly due to limited efficiency and side effects, for example, conventional chemotherapeutics target both cancer cells and normal cells resulting in toxic effects on the body 3 , 4 . (
  • Siva‑1 is a well‑known anti‑apoptosis protein that serves a role in multiple types of cancer cells. (
  • A vincristine (VCR)‑resistant KATO III/VCR gastric cancer cell line with stable Siva‑1 overexpression was established. (
  • The results of the current study revealed that the Siva‑1‑overexpressed KATO III/VCR gastric cancer cells exhibited a significantly decreased sensitivity to VCR, 5‑fluorouracil and doxorubicin. (
  • The current study demonstrated that overexpression of Siva‑1, which functions as a regulator of MDR1 and MRP1 gene expression in gastric cancer cells via promotion of NF‑κB expression, inhibited the sensitivity of gastric cancer cells to certain chemotherapies. (
  • Advanced gastric cancer often recurs and metastasizes subsequent to surgery, and eventually the metastatic cancer cells develop resistance to the chemotherapeutic drugs ( 1 - 3 ). (
  • Cancer cells may become unresponsive to chemotherapeutics via multidrug resistance, which interrupts apoptosis signaling. (
  • Multidrug resistance involves the overexpression of energy-dependent ATP-binding cassette transporter protein, which detoxifies cancer cells and lowers intracellular concentrations under the therapeutic threshold by pumping drugs out at the expense of ATP hydrolysis ( 5 , 6 ). (
  • Therefore, it is necessary to identify multidrug resistant molecules in gastric cancer cells, and to develop more effective diagnostic and therapeutic clinical strategies in order to treat advanced gastric cancer. (
  • Previous studies have demonstrated that Siva-1 arrests apoptosis and facilitates cancer development in osteosarcoma, hepatocellular carcinoma and non-small cell lung cancer ( 15 - 18 ). (
  • From 2011-2014, she was the Division Chief of Pediatric Hematology/Oncology/Stem Cell Transplant/Cancer Biology at Lucile Packard Children?s Hospital at Stanford. (
  • Clinically, Dr. Davis sees patients with leukemia and is involved with the Cancer Cellular Therapies program with experience in treating children with chimeric antigen receptor (CAR) T-cells and other immunotherapies including checkpoint inhibitors. (
  • To address the intrinsic heterogeneity of primary cancers, we have taken a single-cell approach to the study of cancer, particularly childhood leukemia. (
  • Using single-cell, high-parameter analysis platforms, especially mass cytometry, to examine primary patient samples, we seek to identify how childhood cancers diverge from their healthy tissue of origin and how cancer cells may exploit developmental states for their benefit. (
  • APOPTOSIS, a morphologically distinguished type of programmed cell death, is critical not only during development but also in the pathogenesis of a variety of diseases including cancer, autoimmune disease, viral infection, and neurodegenerative disorders. (
  • Precision Cancer Medicine Precision medicine enables cancer specialists to identify and target cancer cells. (
  • The impact of the anti-cancer drugs cisplatin (CDDP) and adriamycin (ADR) was investigated on sensitive and resistant MCF-7-derived human breast cancer cells. (
  • Since Bcl-2 overexpression confers the strongest degree of resistance of MCF-7-derived cells, our observations further highlight Bcl-2 as a prime pharmacological target to sensitize cancer cells to chemotherapeutic agents. (
  • Drug-induced apoptosis is not necessarily dependent on macromolecular synthesis or proliferation in the p53-negative human prostate cancer cell line PC-3: M.M. Borner, et al. (
  • Methods: In our study, it was aimed to evaluate the anti-cancer activity of newly synthesized Platinum (II) [Pt(II)] complex on DU145, LNCaP and PC-3 prostate cancer cell lines. (
  • Natural News ) Researchers from St. George's, University of London have confirmed that cannabinoids are effective in destroying the cells of leukemia, a cancer of blood-forming organs. (
  • When used in conjunction with chemotherapy treatments, cannabinoids, the active chemicals in cannabis, results against the blood cancer cells improved significantly. (
  • Based on their results, the researchers determined that using cannabinoids after chemotherapy improved the chances of cancer apoptosis, or programmed cell death. (
  • Cannabis has scientifically proven properties to inhibit cancer cell growth) and other natural healing remedies plus modern medicine to beat this," said Lattanzi. (
  • Standard chemotherapy cannot eradicate triple-negative breast cancer (TNBC) while the residual cancer cells readily form the vasculogenic mimicry (VM) channels, which lead to the relapse of cancer after treatment. (
  • In hypoxic conditions, the residual cancer cells readily proliferate via the formation of highly patterned VM channels, which provide nutrients to the relapsed cancer cells. (
  • Bioactive phytochemicals are preferential as they pretend differentially on cancer cells only, without altering normal cells. (
  • The cancer phenomenon is described by uncontrolled proliferation and dedifferentiation of a normal cell. (
  • Cancer cells have some marked features i.e., they tune out the signals of proliferation and differentiation, they are capable to sustain proliferation, they overcome the apoptosis, and they have power of invasion and angiogenesis. (
  • Modifications of epigenetic processes involved in cell growth and differentiation also lead to the development of a cancer. (
  • The problem with chemotherapy, at least traditional drugs, is that it does not always target just the cancer cells. (
  • What I mean by that is the chemo drug may not care if it shuts down a dividing body cell or a dividing cancer cell. (
  • True, cancer cells, by their nature, are continually dividing much faster than body cells. (
  • So it would be seem logical to target dividing cells if one were to try to hit cancer cells but not body cells. (
  • In conclusion, telmisartan suppressed the proliferation of human gastric cancer cells by inducing cell cycle arrest. (
  • Authors: Kong FB, Deng QM, Deng HQ, Dong CC, Li L, He CG, Wang XT, Xu S, Mai W Abstract Siva‑1 is a well‑known anti‑apoptosis protein that serves a role in multiple types of cancer cells. (
  • Marinopyrrole A induced apoptosis in Mcl-1-dependent cancer cells and sensitized cancer cells to ABT-737. (
  • The compound has no effect on SM levels in non-cancer cells. (
  • CPI-613 is an E1α pyruvate dehydrogenase (PDH) modulator that prevents cancer cells from metabolizing glucose for energy. (
  • We have found that NDRG2 expression in cervical cancer Hela cells increases significantly upon stimulation with cisplatin, the most popular chemotherapeutic agent currently used for the treatment of advanced cervical cancer. (
  • RT-PCR and Western blot were used to detect expression of NDRG2, Bcl-2 and Bax in cancer cells. (
  • This led us to further explore whether NDRG2 has a role in regulation of cisplatin-sensitivity of cervical cancer cells. (
  • The human cervical cancer cell line Hela was obtained from the American Type Culture Collection (Manassas, VA) and maintained as a monolayer in Dulbecco's modified Eagle's medium (Invitrogen, Carlsbad, CA) supplemented with 10% fetal bovine serum (Sijiqing Biological Engineering Materials Co., Hangzhou, China) at 37°C in the presence of 5% CO 2 -balanced air. (
  • However, some patients do not respond to treatment, or they relapse, often due to additional mutations in their cancer cells. (
  • Nonetheless, they could help pave the way to CML treatment that is customized according to the distinct characteristics of a patient's cancer cells. (
  • In a study published in the journal Leukemia, lead author Ami Patel, MD, Huntsman Cancer Institute researcher and assistant professor in the Division of Hematology and Hematologic Malignancies at the University of Utah, showed that factors produced by bone marrow support cells allowed leukemia cells to survive treatment with quizartinib, a type of TKI. (
  • HDAC inhibitors interfere with HDAC activity and regulate biological events, such as cell cycle, differentiation and apoptosis in cancer cells. (
  • Subsequent profiling of the drug candidates was performed in a panel of ocular cancer cell lines. (
  • The breast cancer cell lines MCF-7, ZR-75-1 and MDA-MB231 were used in this study. (
  • Our data demonstrate that the combination of ABT-737 and radiation-induced apoptosis had an inhibitory effect on breast cancer cell proliferation. (
  • However, treatment with ABT-737 resulted in elevated Mcl-1 in breast cancer cell lines. (
  • Relationship Between Expression of Matrix Metalloproteinase-9 (MMP-9) and Angiogenesis in Renal Cell Carcinoma] Ai Zheng = Aizheng = Chinese Journal of Cancer. (
  • Galectin-3 is an apoptosis-related gene previously found to be over-expressed in invasive tumours and to cause in v itroinvasiveness and metastasis in colon, breast and thyroid follicular cancer cells. (
  • Finally, to establish a role for apoptosis-related and drug resistance-related genes as potential clinical markers in breast cancer, the expression of survivin, galectin-3 and MRP1 genes were examined in breast tumour specimens, by RT-PCR analysis. (
  • Breast cancer cells may have one, both, or none of these receptors. (
  • All the compounds have been tested in combination with generic Imatinib pharmaceutical drug against breast cancer cell lines isolated from Caucasian woman MCF-7, MDA-MB-453 and MCF-10A non-cancer cell lines. (
  • Components of the cell cytoskeleton are therapeutic targets in cancer. (
  • However, no studies have examined the role of betaIV-tubulin in PC or attempted to identify isotype specific roles in regulating cancer cell growth and chemosensitivity. (
  • The over-expression of Hsp90 has been shown in many different cancers this kind of as non-small cell lung cancer, oesophageal squamous cell carcinoma, pancreatic PD184352 carcinoma and superior malignant melanoma. (
  • It truly is well-demonstrated the over-expression of survivin induces resistance to many anti-cancer therapies this kind of as chemotherapy and radiation therapy GDC-0068 in cancer cells. (
  • On top of that, literature exposed that over-expression of survivin attenuated each tamoxifen and cisplatin-induced apoptosis in human breast cancer cells and gastric cancer cells respectively. (
  • Interestingly, a current report suggests that overexpression of survivin may possibly also boost DNA doublestrand breaks repair capability in radiation-treated oral cancer cells by up-regulating the molecular sensor of DNA damage, Ku70. (
  • In clinical scenarios, the degree of survivin expression was shown to become inversely associated with the ranges of apoptosis and positively associated with the danger VX-770 of community tumor recurrence in rectal cancer patients taken care of with radiotherapy. (
  • Interestingly, we also observed an upregulation of survivin in 17-AAG and geldanamycintreated human A549, HONE-1 and HT-29 cancer cells. (
  • We also hypothesize the use of Hsp90 inhibitors could possibly not have the capacity to down-regulate survivin expression in specified cancer cells. (
  • As a result, the function of this study is usually to identify no matter whether focusing on Hsp90 can alter survivin expression differently in numerous cancer cell lines and to examine probable mechanisms that lead to the alteration in survivin expression. (
  • 4 , 5 In addition, the emergence of relapse-specific mutations of cancer cells is often associated with resistance to thiopurines and glucocorticoids. (
  • Preclinical results in the NCI60 cancer cell line panel show that HIV protease inhibitors such as nelfinavir exhibit a wide spectrum of antitumor activity. (
  • They inhibit the proliferation of 60 cancer cell lines derived from nine different tumor types. (
  • MCF-7 human breast cancer cells were used in this study. (
  • The FDA has granted lurbinectedin (PM1183) an orphan drug designation for the treatment of patients with small cell lung cancer (SCLC), according to PharmaMar, the manufacturer of the marine-derived treatment. (
  • We are delighted to receive this orphan drug designation as it underscores the great need for innovative, effective treatments for this cancer, and recognizes the potential benefits that lurbinectedin may provide for patients with small cell lung cancer," Luis Mora Capitán, Managing Director of the Oncology Business Unit of PharmaMar, said in a statement. (
  • Receiving orphan drug designation for the treatment of small cell lung cancer is a significant regulatory milestone in the development of lurbinectedin," Capitán added. (
  • Efficacy and safety of lurbinectedin (PM1183) in small cell lung cancer (SCLC): Results from a phase 2 study. (
  • Chemotherapy often relies on cancer cell death resulting from DNA damage. (
  • Cancer) cells interact with the ECM through a family of receptors called integrins. (
  • Cancer is a condition in which abnormal rapid cell growth due to irregularity in the genome. (
  • Mutations in tumor suppressor genes which work in cell-cycle regulation are often observed in numerous types of cancer (Bukhtoyarov et al. (
  • 2015). Almost 8.8 million people succumbed due to different types of cancer such as lung cancer, liver cancer, breast cancer, stomach cancer, blood cancer etc. ( ). (
  • Small cell lung cancer: Is milk thistle extract the key to defeat? (
  • Small cell lung cancer is an aggressive type of cancer that readily metastasizes to other organs in the body. (
  • The disease can be tough to treat, because the cancer cells often develop resistance to the drugs commonly used against them. (
  • Study shows silibinin, an extract of the milk thistle plant, reverses drug resistance in small cell lung cancer. (
  • Additionally, after incubation with silibinin for 96 hours, the cancer cells showed that their drug resistance to the three chemotherapeutics had reversed. (
  • If further research confirms the findings, small cell lung cancer patients who find their tumors no longer responding to chemotherapy could get a second chance against the disease, leading to longer lives for patients. (
  • Silibinin, a non-toxic natural product, may be useful in treatment of drug-resistant [small cell lung cancer]. (
  • Elucidation of mechanisms regulating cell cycle progression is of fundamental importance for cell and cancer biology. (
  • Januchowski R, Świerczewska M, Sterzyńska K, Wojtowicz K, Nowicki M, Zabel M. Increased Expression of Several Collagen Genes is Associated with Drug Resistance in Ovarian Cancer Cell Lines. (
  • The expression of collagen genes by cancer cells can increase drug resistance by inhibiting the penetration of the drug into the cancer tissue as well as increase apoptosis resistance. (
  • All correlations between the types of cytostatic drugs and the expression levels of different COL genes were studied, and our results suggest that the expression of fibrillar collagens may be involved in the TOP and PAC resistance of the ovarian cancer cells. (
  • The basic reason for the reduced effectiveness of chemotherapy is due to the drug resistance of cancer cells. (
  • mechanisms of drug resistance specific to cancer cells and 2. (
  • We examined whether drugs also inhibit YY1 activity and whether YY1 inhibition correlates with up-regulation of DR5 expression and sensitization of cells to TRAIL-induced apoptosis. (
  • The MCP compounds were identified as inhibitors of Ras-Raf interactions and previously shown to inhibit multiple Ras-dependent transformation phenotypes when used as monoagents in cell culture analyses. (
  • TVA can inhibit NPC cell growth and induced apoptosis through the inhibition of Bad/Akt phosphorylation. (
  • Chen X, Chen XG, Hu X, Song T, Ou X, Zhang C, Zhang W, Zhang C. MiR-34a and miR-203 Inhibit Survivin Expression to Control Cell Proliferation and Survival in Human Osteosarcoma Cells. (
  • BIRC5 and BIRC6 inhibit apoptosis through two different mechanisms: direct interaction with caspase-3 and -7, and regulation of cytokine levels [ 16 , 17 ]. (
  • Synergistic combination therapy with cotyleninxa0A and vincristine in multiple myeloma models. (
  • The synergistic activity of MCP110 and paclitaxel was further established by experiments showing that in Kaposi's sarcoma oncogenically transformed cell lines, cellular models for tumors treated with taxanes in the clinic and in which Raf-dependent signaling plays an important role, MCP110 synergizes with paclitaxel and limit growth. (
  • Interestingly, we observed a synergistic effect of SKi with the classical chemotherapeutic drug vincristine. (
  • Cellular apoptosis (ie, programmed cell death) is another potential mechanism of many antineoplastic agents. (
  • When this drug is used as an alkylating agent, the mechanism of action of its active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells. (
  • Vcr-R cell resistance seemed to rely on a different mechanism, since it was found to be independent of Bcl-2 expression. (
  • However, the exact mechanism of this interaction between vincristine and STI-571 was not further investigated. (
  • Unravelling the mechanism of pterostilbene-induced cell apoptosis in this cell line could help in the development of a targeted therapy. (
  • Studies in a wide range of cellular models showed that this combination effect was not observed in cells overexpressing P-glycoprotein and that the mechanism involved was not inhibition of P-glycoprotein. (
  • The aim of this study was to investigate the effect of Wnt5a on the vincristine (VCR) resistance in human ovarian carcinoma SKOV3 cells and its possible mechanism. (
  • Caspase-3 activation studies provided an insight into the mechanism of action of cardenolides in retinoblastoma cells. (
  • The mechanism of action was reported by induced apoptosis and tested by a DNA enzyme inhibitor experiment (ELISA) for Methyl Transferase. (
  • Yet, the mechanism with the over-expression of survivin in such cell line was unknown. (
  • 3 ] Although the mechanism of action of ABT-751 is similar to that of vincristine, ABT-751 binds to a different site on β-tubulin and is not a substrate for multi-drug resistance mediated by P-glycoprotein. (
  • Finally, in vivo testing indicate that MCP110 is bioavailable, inhibits the growth of LXFA 629 lung and SW620 colon carcinoma cells in xenograft models, and again strongly synergizes with paclitaxel. (
  • METHODS: Cultured NB4 cells were treated with As2O3, paclitaxel, and vincristine. (
  • Similar results were obtained in K562 CML cells using lead MTAs (paclitaxel and nocodazole) in combination with STI-571. (
  • In addition, the effects of matrine on cell apoptosis, proliferation and cell cycle staging together with its potential underlying mechanisms were investigated. (
  • ConclusionHere we showed that ergolide could be considered as a potent natural compound against leukemic cells by inducing cell cycle arrest followed by dose-dependent cell death. (
  • Some agents act at specific phases of the cell cycle, whereas others (ie, alkylating agents, anthracyclines, cisplatin) are not phase-specific. (
  • The parameters examined included cell cycle distribution, loss of mitochondrial membrane potential (MMP), DNA fragmentation and reactive oxygen species (ROS) generation. (
  • In this study, a genome-wide expression analysis of cell cycle- and apoptosis-related genes in corticosteroid-, vincristine-, and melphalan-resistant U-266 multiple myeloma cell lines was conducted. (
  • Among the cell cycle- and apoptosis-related gene expressions, alterations of more than 2-fold were considered significant. (
  • Through exogenous expression analyses, we found that PDCD2 and NCoR1 can decrease proliferation, and increase apoptosis and G1 cell cycle arrest, in GIST-derived cells. (
  • Methods: REH, NALM-6, MOLT4 and Jurkat cell lines were treated with varied doses of DTCM-g (2.5 to 20ug/mL) and analyzed in terms of growth (Resazurin reduction), apoptosis (caspase-activation) and cell cycle dynamics. (
  • In parallel, DTCM-g treatment mediated a significant increase in apoptosis and arrest at the G1 stage of the cell cycle. (
  • Polo-like kinase 1 was necessary for leukemic cell survival, since short hairpin-mediated Polo-like kinase 1 knockdown in acute lymphoblastic leukemia cell lines inhibited cell proliferation by G2/M cell cycle arrest and induced apoptosis through caspase-3 and poly (ADP-ribose) polymerase cleavage. (
  • In apoptosis induced by γ-irradiation and cisplatin, two antitumor treatments that are cell-cycle phase-nonspecific agents, both Bcl-XL and Bcl-2 conferred similar protection against γ-irradiation, but Bcl-XL provided better protection than Bcl-2 against cisplatin. (
  • Blocks the cell cycle at G1/S phase. (
  • Dissociation of nuclear and cytoplasmic cell cycle progression by drugs employed in cell synchronization: L. Urbani, et al. (
  • Cell cycle analysis revealed a clear decrease in G1-cells and an increase in G2/M-cells indicating an arrest in mitosis. (
  • Cell cycle analysis of propidium iodide-stained cells showed that STI-571 significantly reduced PBOX-6-induced G 2 M arrest and polyploid formation with a concomitant increase in apoptosis. (
  • Flow cytometric analysis was used to determine the cell cycle distribution of these test compounds in DLKP-SQ, a human lung carcinoma clonal cell line. (
  • There was no apparent effect on the cell cycle distribution using A-l (inactive) or N-l (active). (
  • DLKP-SQ treated with 5-fluorouracil alone and in combination showed no effect on cell cycle distribution. (
  • Toxicity elicited by the antitumor compound taxol has been linked to irreversible tubulin polymerization, cell cycle block at mitosis, and cell death from apoptosis. (
  • We have used pulsed drug exposure of synchronized populations to identify two points, one in transition from G0 to G1 and the other at G2/M of cell cycle, that are most sensitive to taxol-induced cell killing. (
  • thus, cell cycle progression appeared requisite for cell death. (
  • Conversely, overexpression of wildtype PLK1 promoted cell cycle progression in cells treated with taxol. (
  • When compared to individual agents, the combination of TA and VCR increased MB cell growth inhibition, induced apoptosis and caused cell cycle (G 2 /M phase) arrest. (
  • Conversely, accelerated cell cycle progression and compromised repair in the absence of Rb and p53 may lead to accumulation of DNA damage, causing sensitization to therapy. (
  • An methylthio-trans-stilbene (2,4,5-MTS) was analyzed analysis of cell cycle distribution showed a significant and compared with the effect of trans-resveratrol. (
  • By disrupting the dynamic equilibrium of microtubules, ABT-751 interferes with functions critical to cellular structure, motility, intracellular transport, and chromosome alignment and segregation during mitosis [ 1 , 2 ] resulting in cell cycle arrest in the G 2 /M phase and apoptosis. (
  • Based on gene ontology biological process annotation, the upregulated genes were most enriched in cell cycle processes (enrichment score = 15.3), whilst the downregulated genes were clustered in transcription regulation (enrichment score = 12.6). (
  • Elevated expression of cell cycle regulators (e.g kinesins, AURKA , CDK s) was the key genetic defect implicated in relapsed ALL, and serve as attractive targets for therapeutic intervention. (
  • Peripheral T-cell lymphomas (PTCLs) are neoplasias from post-thymic T-cells at different stages of differentiation and are a heterogeneous group of malignancies which present with different morphological patterns, phenotypes, and clinical presentations. (
  • TrkA neurogenic receptor regulates differentiation of neuroblastoma cells: W. Poluha, et al. (
  • Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. (
  • These alterations include mutations in DNA repair genes, tumor suppressor genes, oncogenes and genes involve in cell growth & differentiation. (
  • Several genes coordinate together for the growth & differentiation of a normal cell. (
  • The biological activity of epoetin alfa mimics human urinary EPO, which stimulates division and differentiation of committed erythroid progenitor cells and induces the release of reticulocytes from bone marrow into the blood stream. (
  • NDRG2, a member of N-Myc downstream regulated gene family, plays some roles in cellular stress, cell differentiation and tumor suppression. (
  • This has been implicated as a necessary component of intracellular signaling to elicit a range of cellular responses including mitogenesis, differentiation, and cell survival [1]. (
  • Apoptosis is a fundamental process that regulates development and cell differentiation [ 9 , 10 ]. (
  • However, matrine was not able to increase the sensitivity of cells to VCR. (
  • BH3 profiling identifies cells that require BCL-2 for survival and predicts sensitivity to the BCL-2 antagonist ABT-737. (
  • Inhibition of KIT increases sensitivity of these cells to DXR and VCR. (
  • Bcl-2 and its homologue Bcl-XL are expressed in a variety of tumors and their expression modulates the sensitivity of tumor cells to a wide spectrum of chemotherapeutic agents and γ-irradiation. (
  • These data suggested that down-regulation of NDRG2 could enhance sensitivity of Hela cells to cisplatin through inhibiting Bcl-2 protein expression, which might be mediated by up-regulating miR-15b and miR-16. (
  • WNT5A gene silencing significantly increased the sensitivity of SKOV3/VCR cells to VCR, the IC of VCR being decreased from 38.412 to 9.283 mg/L (P (
  • In the current study, we evaluated the biological effects of survivin knockdown on osteosarcoma cell proliferation, colony formation rate, and sensitivity to the chemotherapeutic agent cisplatin. (
  • Small molecule XIAP inhibitors enhance TRAIL-induced apoptosis and antitumor activity in preclinical models of pancreatic carcinoma. (
  • Confocal fluorescence microscopy data showed that echinatin significantly induced autophagy in ESCC cells, and autophagy inhibitor bafilomycinA1 attenuated the suppressive effects of echinatin on cell viability and apoptosis. (
  • Specific DNA polymerase alpha and delta inhibitor in eukaryotic cells and in some viruses of animal origin. (
  • Apoptosis inhibitor/inducer. (
  • Interactions between the Bcr-Abl kinase inhibitor STI-571 (imatinib mesylate) and a novel microtubule-targeting agent (MTA), pyrrolo-1,5-benzoxazepine (PBOX)-6, were investigated in STI-571-sensitive and -resistant human chronic myeloid leukemia (CML) cells. (
  • Meanwhile, LY294002 (PI3K inhibitor) decreased the protein expression levels of MDR1, β-catenin and Survivin, as well as the phosphorylation levels of Akt and GSK3β in SKOV3/VCR cells (P (
  • A novel, selective small molecule inhibitor of IKK-2, ML120B ( N -[6-chloro- 7 -methoxy- 9H -β-carbolin-8-yl]-2-methylnicotinamide) was used to perturb NF-κB in lymphoma cells. (
  • To gain mechanistic insights into microtubule inhibitor-induced cell death, the role of the mitotic kinase PLK1 was addressed. (
  • Not like other IAPs, survivin is usually a bifunctional protein that functions being a important regulator of mitosis and inhibitor of programmed cell death. (
  • In the present study, we demonstrate a highly increased response of various acute leukemia cell lines, drug-resistant cells and patient-derived xenograft cells by combining the recently introduced protein disulfide isomerase inhibitor PS89 with cytostatics. (
  • KIFC3 has minus end-directed microtubule motor activity and functions in Golgi positioning and integration ( 18 ) and also in apical transport in epithelial cells ( 19 ). (
  • Microtubules are nucleated and organized by microtubule organizing centers (MTOCs), such as the centrosome found in the center of many animal cells or the basal bodies found in cilia and flagella, or the spindle pole bodies found in most fungi. (
  • Tubulin and microtubule-mediated processes, like cell locomotion, were seen by early microscopists, like Leeuwenhoek (1677). (
  • In this study, we investigated how As2O3 induces apoptosis by causing microtubule dysfunction. (
  • Immunocytochemistry revealed changes in the cellular microtubule network and formation of polymerized microtubules in As2O3-treated cells. (
  • Currently, little information is available concerning the effects of simultaneously causing microtubule disruption while inhibiting tyrosine kinase activity in CML cells. (
  • TA-induced inhibition of survivin expression potentially destabilizes mitotic microtubule assembly, sensitizing MB cells and enhancing the efficacy of VCR. (
  • Remarkably, inhibition of apoptosis in sensitive cell lines by caspase inhibition promoted polyploidy confirming the inverse relationship between apoptosis and polyploidization. (
  • In recent decades, numerous studies have indicated a number of factors, such as negative expression of the retinoblastoma gene ( Rb ) and the tumor suppressor p53, bone dysplasia, and inhibition of apoptosis, that are associated with a high risk of osteosarcoma development [ 2 - 8 ]. (
  • Cotylenin A and vincristine synergistically inhibited the growth and induced apoptosis in myeloma cells. (
  • Acts synergistically with vincristine and doxorubicin. (
  • Vincristine works partly by binding to the tubulin protein, stopping the tubulin dimers from polymerizing to form microtubules, causing the cell to be unable to separate its chromosomes during the metaphase. (
  • Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. (
  • RESULTS: As2O3 treatment disrupted tubulin assembly resulting in dysfunctional microtubules that cause death in APL cells. (
  • CONCLUSION: The microtubules alterations found with As2O3 treatment suggest that As2O3 increases the depolymerized forms of tubulin in cells and that this is potentially due to arsenite's negative effects on spindle dynamics. (
  • Dosing of conventional vincristine is limited by significant neurotoxicity due to binding to neuronal tubulin, with such toxicity occurring at doses higher than 1.4 mg/m 2 and leading to capping of the total dose of vincrsitine. (
  • PC cells (MiaPaCa-2, HPAF-II, AsPC1) were treated with siRNA (control, betaIVa-tubulin or betaIVb-tubulin). (
  • Inhibition of betaIVa-tubulin in PC cells had no effect chemosensitivity. (
  • We show for the first time that betaIVb-tubulin, but not betaIVa-tubulin, plays a role in regulating vinca alkaloid chemosensitivity in PC cells. (
  • This issue is further exacerbated by the development of leukemic cell chemoresistance, which has been demonstrated for several cytostatics including tubulin binders and topoisomerase inhibitors. (
  • Following drug exposure, polymerized tubulin decreased in a concentration and time dependent manner in cell lines. (
  • 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. (
  • Combined treatment with cotylenin A and vincristine induced autophagy (formation of LC3-II and degradation of p62 protein). (
  • In principle, the method is capable of identifying any protein or RNA whose overexpression in a mutant cell line confers a selectable phenotype ( 10 ). (
  • The B-cell-specific surface marker CD20 ( 3 ) does not circulate in the plasma as a free protein, which could potentially block antibody binding to the cells ( 4 ). (
  • Siva-1 exists in a wide variety of tissues and cells, and serves as a proapoptotic protein ( 7 ). (
  • This analysis showed that MCP compounds inhibited Ras-induced activation of the Raf and ERK mitogen-activated protein kinase (MAPK) signaling cascade, Ras-induced cell migration, morphologic changes and anchorage-independent growth, and Ras-regulated expression of matrix metalloproteases and cyclin D1 ( 7 ). (
  • High Polo-like kinase 1 protein phosphorylation, but not expression, was associated with a lower probability of event-free survival ( P =0.042) and was a borderline significant prognostic factor ( P =0.065) in a multivariate analysis including age and initial white blood cell count. (
  • Fas-induced apoptosis can be effectively blocked at several stages by either FLICE-inhibitory protein (FLIP), by Bcl-2, or by the cytokine response modifier A (CrmA). (
  • Inhibition of NDRG2 in Hela cells was accompanied by decreased Bcl-2 protein level. (
  • Analysis of antiapoptotic protein expression revealed that IL-4 stimulation resulted in up-regulation of cellular (c) FLIP/FLAME-1 and Bcl-x L . Exogenous expression of cFLIP/FLAME-1 inhibited apoptosis induced by CD95 and to a lesser extent by chemotherapy, while tumor cells transduced with Bcl-x L were substantially protected both from CD95 and chemotherapeutic drug stimulation. (
  • The cFLIP/FLAME-1 protein, also called caspase homolog, Casper, caspase-like apoptosis regulatory protein, I-FLICE, MACH-related inducer of toxicity, and Usurpin, is structurally similar to caspase-8 as it contains two death effector domains and a caspase-like domain, but lacks the key residues for proteolysis, most notably the cysteine within the active site ( 7 ). (
  • The result showed that SKOV3/VCR cells had significantly higher protein expression levels of Wnt5a, MDR1, Survivin and β-catenin, phosphorylation levels of Akt and GSK3β, and mRNA expression level of Wnt5a, compared with SKOV3 cells (P (
  • Regulative Function of Extracelluar Regulated Protein Kinases and Telomerase in Apoptosis of Hepatocarcinomatous Cell SMMC-7721] Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology. (
  • Survivin protein expression was dramatically down-regulated in DLKP-vincristine and DLKP-taxotere MDR variants. (
  • This decrease was not observed at the mRNA level, indicating that this down-regulation of survivin protein may be at the post-transcriptional level in this cell system. (
  • Molecular 'switch' reverses chronic inflammation and aging - Science Daily, 2/6/20 - 'By studying mice and immune cells called macrophages, the team found that a protein called SIRT2 is responsible for deacetylating the NLRP3 inflammasome. (
  • Thus, both of the microalgae in dietary supplements will be effective mediators in scavenging free radicals, inhibiting human pathogens and antiapoptotic protein of tumor cells. (
  • Western blot analysis showed very high expression levels of COL3A1 protein, and immunocytochemistry analysis showed the presence of extracellular COL3A1 in the W1TR cell line. (
  • Among those gene expressions, the most drastic increase in cyclin E2 could be important for the survival of vincristine-resistant U-266 cell lines, whereas alteration of ceramide metabolism genes could be important in melphalan resistance. (
  • MAP4K4 Inhibition Promotes Survival of Human Stem Cell-Derived Cardiomyocytes and Reduces Infarct Size In Vivo. (
  • Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with poor survival. (
  • Recent studies suggest that the T-cell phenotype is an independent significant prognostic factor, with PTCLs having one of the lowest overall survival and failure-free survival rates. (
  • As a condition of the accelerated approval, the manufacturer (Talon Therapeutics, Inc), must evaluate the effect of liposomal vincristine on overall survival in a randomized controlled trial in adult patients with ALL. (
  • Akt inhibits apoptosis by phosphorylating the Bcl-2 family member Bad, which then interacts with 14-3-3 and dissociates from Bcl-x L allowing for cell survival. (
  • Alternatively, Akt activates IKK-α that ultimately leads to NF-κB activation and cell survival. (
  • We recently proposed that Th1 and Th2 cytokines exert opposite effects on the pathogenesis and clinical outcome of organ-specific autoimmunity by altering the expression of genes involved in target cell survival. (
  • IKK-2 is an important regulator of the nuclear factor-κB (NF-κB) which has been implicated in survival, proliferation and apoptosis resistance of lymphoma cells. (
  • Pioglitazone, a full PPARγ agonist, improved the survival of patients by the gradual elimination of the residual CML stem cell pool. (
  • Survival has been improved mainly in younger patients below the age of 65 with the advent of high-dose melphalan therapy followed by autologous stem cell transplantation (ASCT). (
  • Besides their essential role in cell adhesion, integrins are important for providing survival and proliferative signals through extensive cross talk with growth factor receptors ( Yamada and Even-Ram, 2002 ). (
  • In addition, we reported that SKi affected signaling cascades implicated in survival, proliferation and stress response of cells. (
  • Cell-division rates vary for different tumors. (
  • Dual-specific chimeric antigen receptor T cells and an indirect vaccine eradicate a variety of large solid tumors in an immunocompetent, self-antigen setting. (
  • Liposomal encapsulation of vincristine prolongs circulation of active drug and passively targets it to tissues with fenestrated vasculature (eg, bone marrow, lymph nodes, spleen, liver, and solid tumors), resulting in increased penetration and accumulation in tumor tissue and potentially reducing levels in neural tissue compared with free vincristine. (
  • To date, the FDA has approved three HDAC inhibitors for cutaneous/peripheral T-cell lymphoma and many more HDAC inhibitors are in different stages of clinical development for the treatment of hematological malignancies as well as solid tumors. (
  • Small molecule XIAP inhibitors sensitize childhood acute leukemia cells for CD95-induced apoptosis. (
  • Small-molecule XIAP inhibitors enhance gamma-irradiation-induced apoptosis in glioblastoma. (
  • Survivin is usually a member in the inhibitors of apoptosis household. (
  • These results elucidate the molecular mechanisms by which Wnt/β-catenin inhibits apoptosis and provide new insight into Wnt signaling-mediated oncogenesis. (
  • The present study aimed to investigate the effects of matrine on vincristine (VCR)‑resistant retinoblastoma (RB) cells and to assess the underlying mechanisms governing this effect. (
  • Finally, the mechanisms of action of PDCD2 and NCoR1 in GIST-derived cells were determined using immunoprecipitation and Western blotting assays. (
  • Nonetheless, the contribution of these mechanisms on primary normal and malignant B-cells in vivo and the molecular mechanisms of rituximab action need to be defined. (
  • Therefore, the development of effective antiapoptotic mechanisms can result in malignant cell resistance to immune reaction and therapy ( 4 ). (
  • The present study aims to investigate the antiproliferative activity on HEp 2 cells by the water extract of S. parvifolia leaves and to evaluate potential mechanisms. (
  • Mitochondrial permeability is also related to the increased generation of reactive oxygen species (ROS), which plays a role in the degradation phase of apoptosis (i.e. plasma membrane alterations). (
  • They are also involved in cell division (by mitosis and meiosis) and are the major constituents of mitotic spindles, which are used to pull eukaryotic chromosomes apart. (
  • Whereas some cells (for example, cardiac and skeletal muscle fibers, CNS neurons) last a lifetime, others (for example, epithelial and glandular cells, erythrocytes) have limited life-spans, at the end of which they are genetically programmed for self-destruction by apoptosis, usually to be replaced by others formed by mitosis from surviving cells. (
  • The histology showed round cells with hyper chromatic nuclei and pleomorphisms, eosinophilic cytoplasm, very frequent mitosis, apoptosis, and focal necrosis. (
  • The overuse of vincristine may also lead to drug resistance by overexpression of the p-glycoprotein pump (Pgp). (
  • There is an attempt to overcome resistance by the addition of derivatives and substituents to the vincristine molecule. (
  • Several chemotherapeutic drugs in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) result in reversal of resistance to TRAIL-mediated apoptosis through up-regulation of DR5 expression. (
  • Hence, YY1 may be a potential therapeutic target to reverse resistance to TRAIL-induced apoptosis. (
  • To recapitulate various aspects of acquired resistance, rituximab-resistant (RR) clones were established from lymphoma lines and compared with parental cells. (
  • Further, what populations or features of tumor cells are associated with clinical outcomes of interest, such as site of disease, relapse, or drug resistance? (
  • Resistance to cisplatin and adriamycin is associated with the inhibition of glutathione efflux in MCF-7-derived cells. (
  • In addition to the beneficial effects associated with apoptosis, inappropriate apoptosis contributes to the pathogenesis and drug resistance of human leukemias and lymphomas (Cohen, J. J., et al. (
  • Apoptosis resistance is the major cause of chemotherapy failure in most kinds of cancers, including Burkitt lymphomas (BL). (
  • To determine whether survivin over-expression plays a role in drug-resistance, transient transfections of survivin cDN into SKOV-3 'Tet off , MCF-7 'Tet off and DLKP cells, were carried out. (
  • To further investigate the role o f galectin-3 and survivin in drug resistance and invasiveness, RT-PCR and western blot analysis were carried out on DLKP and RPMI- 2650 cells which had been exposed to sequential pulsing with three (vincristine, taxotere and 5-fluorouracil) and five (vincristine, 5-fluorouracil, CCNU, carboplatin and epirubicin) chemotherapy drugs, respectively. (
  • In the present study, we investigated the characteristics of FaDu cells (a hypopharyngeal carcinoma cell line) with multidrug resistance (MDR) induced by Taxol. (
  • Compared with the FaDu cells, the drug resistance of FaDu/T cells to DDP, 5-FU, Dox and VCR was increased 8.99-, 21.96-, 31.42- and 10.00-fold, respectively. (
  • Therapeutic opportunities for counteracting apoptosis resistance in childhood leukaemia. (
  • 0.01), thus inhibiting macrophage cell viability and inducing apoptosis. (
  • Our study indicates that signal transduction and mitochondrial ATP production are essential during adaptation of leukemic cells to vincristine, these processes represent potential therapeutic targets. (
  • The findings of this study promote PS89 as a novel chemosensitizing agent for the treatment of acute leukemia and uncovers that targeting the endoplasmic reticulum - mitochondrial network of cell death is a promising approach in combination therapy. (
  • Conclusions: We have demonstrated for the first time that the vincristine from Eutypella spp - CrP14 is an efficient inducer of apoptosis in A431 cells, meriting its further evaluation in vivo. (
  • Leukemic blast cells accumulate ara-GTP, which allows for incorporation into DNA, leading to inhibition of DNA synthesis and cell death. (
  • The nanoparticle targets only leukemic cells and therefore would reduce the severe adverse effects of current treatments. (
  • 2018. Crystal structures and human leukemic cell inducible activities of parthenolide analogues isolated from Piptocoma rufescens. (
  • Unrestrained proliferation of myeloid leukemic cells causes displacement of normal hematopoietic cells and lymphoblasts' infiltration to the lymph nodes, spleen, liver and other organs [2]. (
  • Remission consolidation follows and is aimed at eliminating residual leukemic cells. (
  • The binding of kinesins to microtubules opposes the stabilizing effect of docetaxel that prevents cytokinesis and leads to apoptosis. (
  • Together, these findings highlight the potential clinical benefits in simultaneously targeting the microtubules and the Bcr-Abl oncoprotein in STI-571-sensitive and -resistant CML cells. (
  • Our results suggest that the combination of cotylenin A and vincristine may have therapeutic value. (
  • Within the next areas, a synopsis of evaluation of therapeutic and aromatic plant life (MAPs) relating to their antioxidant and oxidative stress-modulating properties in cancers cell lines is certainly presented. (
  • Therapeutic efficacy and histological changes after bacillus Calmette-Guerin (BCG), vincristine and BCG/vincristine combination therapy of canine transmissible venereal tumours (CTVT) were studied. (
  • Thus, agents that are useful to modulate apoptosis are potentially useful as therapeutic agents for treating diseases in which inappropriate apoptosis is implicated. (
  • As a result, there is a considerable amount of ongoing research devoted to the identification of molecular regulators of apoptosis, and there is currently a need for novel agents (e.g. chemical or biological), and novel therapeutic methods, that are useful for modulating apoptosis. (
  • Human rhabdomyosarcoma cells express functional pituitary and gonadal sex hormone receptors: Therapeutic implications. (
  • Zhao B, Li B, Liu Q, Gao F, Zhang Z, Bai H and Wang Y: Effects of matrine on the proliferation and apoptosis of vincristine‑resistant retinoblastoma cells. (
  • ROS have been implicated in the regulation of diverse cellular functions including defense against pathogens, intracellular signaling, transcriptional activation, proliferation, and apoptosis. (
  • The liposome encapsulation of vincristine enhances the efficacy of the vincristine drug while simultaneously decreasing the neurotoxicity associated with it. (
  • Liposome encapsulation increases vincristine's plasma concentration and circulation lifetime in the body, and allows the drug to enter cells more easily. (
  • In August 2012, vinCRIStine sulfate LIPOSOME injection (Marqibo) was granted accelerated approval for the treatment of adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more antileukemia therapies. (
  • The newly approved vincristine product is a sphingomyelin/cholesterol liposome-encapsulated formulation of vincristine sulfate. (
  • Nelarabine was approved by the US Food and Drug Administration [FDA] as an orphan drug to treat T-cell lymphoblastic lymphoma (a type of non-Hodgkin lymphoma [NHL]) that does not respond or that relapses with at least 2 chemotherapy regimens. (
  • Dickinson, M. Durable clinical remission induced by romidepsin for chemotherapy-refractory peripheral T-cell lymphoma with central nervous system involvement. (
  • The course of anxiety, depression and unmet needs in survivors of Diffuse Large B Cell Lymphoma and Multiple Myeloma in the early survivorship period. (
  • Denileukin Diftitox for the treatment of cutaneous T cell lymphoma. (
  • Romidepsin for treating cutaneous T-cell lymphoma. (
  • Responses to Romidepsin by Line of Therapy in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma. (
  • Brentuximab vedotin or Physician's Choice in CD30-positive Cutaneous T-Cell Lymphoma. (
  • Follicular (WSU-FSCCL) and Diffuse Large Cell (WSU-DLCL2) Lymphoma, both of which constitutively express p-IκB. (
  • Clinically, grade 3B follicular lymphoma is treated like diffuse large B-cell lymphoma . (
  • Down-regulation of NDRG2 didn't influence the colony-forming ability but promoted cisplatin-induced apoptosis of Hela cells. (
  • Activation of p34cdc2 coincident with taxol-induced apoptosis -- Donaldson et al. (
  • Further, in sensitive cell lines taxol-induced apoptosis was accompanied by caspase activation, Bid cleavage and Mcl-1 down-regulation. (
  • The resistant cell line, FaDu/T, was grown by exposing normal FaDu cells to escalating concentrations of Taxol stepwise for over 12 months. (
  • Antineoplastic agents interfere with cell reproduction. (