Clonal Evolution: The process of accumulation of genetic and epigenetic changes over time in individual cells and the effect of the changes on CELL PROLIFERATION.Neoplastic Stem Cells: Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Antigens, CD24: A cell adhesion protein that was originally identified as a heat stable antigen in mice. It is involved in METASTASIS and is highly expressed in many NEOPLASMS.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Antigens, CD44: Acidic sulfated integral membrane glycoproteins expressed in several alternatively spliced and variable glycosylated forms on a wide variety of cell types including mature T-cells, B-cells, medullary thymocytes, granulocytes, macrophages, erythrocytes, and fibroblasts. CD44 antigens are the principle cell surface receptors for hyaluronate and this interaction mediates binding of lymphocytes to high endothelial venules. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)Spheroids, Cellular: Spherical, heterogeneous aggregates of proliferating, quiescent, and necrotic cells in culture that retain three-dimensional architecture and tissue-specific functions. The ability to form spheroids is a characteristic trait of CULTURED TUMOR CELLS derived from solid TUMORS. Cells from normal tissues can also form spheroids. They represent an in-vitro model for studies of the biology of both normal and malignant cells. (From Bjerkvig, Spheroid Culture in Cancer Research, 1992, p4)Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.Retinal Dehydrogenase: A metalloflavoprotein enzyme involved the metabolism of VITAMIN A, this enzyme catalyzes the oxidation of RETINAL to RETINOIC ACID, using both NAD+ and FAD coenzymes. It also acts on both the 11-trans- and 13-cis-forms of RETINAL.Adult Stem Cells: Cells with high proliferative and self renewal capacities derived from adults.Embryonic Stem Cells: Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.Stem Cell Transplantation: The transfer of STEM CELLS from one individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or between species (XENOTRANSPLANTATION), or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells determines their potency or pluripotency to differentiate into various cell types.Clone Cells: A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. This enzyme was formerly classified as EC 1.1.1.70.Cell Line, Tumor: A cell line derived from cultured tumor cells.Stem Cell Niche: A particular zone of tissue composed of a specialized microenvironment where stem cells are retained in a undifferentiated, self-renewable state.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Side-Population Cells: A group of cells identified on FLOW CYTOMETRY profiles as distinct from the main group of cells by their ability to extrude the fluorescent dye Hoechst 33342, often a characteristic property of less differentiated progenitor and STEM CELLS.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Mice, SCID: Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Pluripotent Stem Cells: Cells that can give rise to cells of the three different GERM LAYERS.Chromosome Aberrations: Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.Epithelial-Mesenchymal Transition: Phenotypic changes of EPITHELIAL CELLS to MESENCHYME type, which increase cell mobility critical in many developmental processes such as NEURAL TUBE development. NEOPLASM METASTASIS and DISEASE PROGRESSION may also induce this transition.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Mice, Inbred NOD: A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.Cell Lineage: The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.Tumor Markers, Biological: Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Breast Neoplasms: Tumors or cancer of the human BREAST.Neural Stem Cells: Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Hematopoietic Stem Cell Transplantation: Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.Leukemia, Myelogenous, Chronic, BCR-ABL Positive: Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.Transplantation, Heterologous: Transplantation between animals of different species.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Octamer Transcription Factor-3: An octamer transcription factor that is expressed primarily in totipotent embryonic STEM CELLS and GERM CELLS and is down-regulated during CELL DIFFERENTIATION.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Induced Pluripotent Stem Cells: Cells from adult organisms that have been reprogrammed into a pluripotential state similar to that of EMBRYONIC STEM CELLS.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cell SeparationKaryotyping: Mapping of the KARYOTYPE of a cell.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Mesenchymal Stromal Cells: Bone-marrow-derived, non-hematopoietic cells that support HEMATOPOETIC STEM CELLS. They have also been isolated from other organs and tissues such as UMBILICAL CORD BLOOD, umbilical vein subendothelium, and WHARTON JELLY. These cells are considered to be a source of multipotent stem cells because they include subpopulations of mesenchymal stem cells.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.SOXB1 Transcription Factors: A subclass of SOX transcription factors that are expressed in neuronal tissue where they may play a role in the regulation of CELL DIFFERENTIATION. Members of this subclass are generally considered to be transcriptional activators.Benzamides: BENZOIC ACID amides.Neoplasm Metastasis: The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Multipotent Stem Cells: Specialized stem cells that are committed to give rise to cells that have a particular function; examples are MYOBLASTS; MYELOID PROGENITOR CELLS; and skin stem cells. (Stem Cells: A Primer [Internet]. Bethesda (MD): National Institutes of Health (US); 2000 May [cited 2002 Apr 5]. Available from: http://www.nih.gov/news/stemcell/primer.htm)Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.Mesenchymal Stem Cell Transplantation: Transfer of MESENCHYMAL STEM CELLS between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS).Xenograft Model Antitumor Assays: In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.Brain Neoplasms: 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.Stem Cell Factor: A hematopoietic growth factor and the ligand of the cell surface c-kit protein (PROTO-ONCOGENE PROTEINS C-KIT). It is expressed during embryogenesis and is a growth factor for a number of cell types including the MAST CELLS and the MELANOCYTES in addition to the HEMATOPOIETIC STEM CELLS.Tumor Microenvironment: The milieu surrounding neoplasms consisting of cells, vessels, soluble factors, and molecules, that can influence and be influenced by, the neoplasm's growth.Colonic Neoplasms: Tumors or cancer of the COLON.MicroRNAs: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.Pancreatic Neoplasms: Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.In Situ Hybridization, Fluorescence: A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.Ovarian Neoplasms: Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Receptors, Notch: A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN repeats in their cytoplasmic domains. The cytoplasmic domain of notch receptors is released upon ligand binding and translocates to the CELL NUCLEUS where it acts as transcription factor.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.PiperazinesMolecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Molecular Targeted Therapy: Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Prostatic Neoplasms: Tumors or cancer of the PROSTATE.Neoplasm Invasiveness: Ability of neoplasms to infiltrate and actively destroy surrounding tissue.Immunogenetic Phenomena: GENETIC PHENOMENA characterizing IMMUNITY and the immune response.DNA, Neoplasm: DNA present in neoplastic tissue.Philadelphia Chromosome: An aberrant form of human CHROMOSOME 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 per cent of patients with chronic myelocytic leukemia (LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE).Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Lung Neoplasms: Tumors or cancer of the LUNG.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Cell Culture Techniques: Methods for maintaining or growing CELLS in vitro.Cell Dedifferentiation: A reverse developmental process in which terminally differentiated cells with specialized functions revert back to a less differentiated stage within their own CELL LINEAGE.Leukemia, Lymphocytic, Chronic, B-Cell: A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.Heterografts: Tissues, cells or organs transplanted between animals of different species.Radiation Tolerance: The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.Chromosome Disorders: Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429)Tumor Stem Cell Assay: A cytologic technique for measuring the functional capacity of tumor stem cells by assaying their activity. It is used primarily for the in vitro testing of antineoplastic agents.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.Blast Crisis: An advanced phase of chronic myelogenous leukemia, characterized by a rapid increase in the proportion of immature white blood cells (blasts) in the blood and bone marrow to greater than 30%.Cytogenetic Analysis: Examination of CHROMOSOMES to diagnose, classify, screen for, or manage genetic diseases and abnormalities. Following preparation of the sample, KARYOTYPING is performed and/or the specific chromosomes are analyzed.beta Catenin: A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Immunoglobulin Heavy Chains: The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Stem Cell Research: Experimentation on STEM CELLS and on the use of stem cells.Early Detection of Cancer: Methods to identify and characterize cancer in the early stages of disease and predict tumor behavior.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Neoplasms, Glandular and Epithelial: Neoplasms composed of glandular tissue, an aggregation of epithelial cells that elaborate secretions, and of any type of epithelium itself. The concept does not refer to neoplasms located in the various glands or in epithelial tissue.Plant Stems: Parts of plants that usually grow vertically upwards towards the light and support the leaves, buds, and reproductive structures. (From Concise Dictionary of Biology, 1990)Survival Analysis: 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.MCF-7 Cells: An estrogen responsive cell line derived from a patient with metastatic human breast ADENOCARCINOMA (at the Michigan Cancer Foundation.)Fetal Stem Cells: Cells derived from a FETUS that retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.Carcinogenesis: The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years.Wnt Signaling Pathway: A complex signaling pathway whose name is derived from the DROSOPHILA Wg gene, which when mutated results in the wingless phenotype, and the vertebrate INT gene, which is located near integration sites of MOUSE MAMMARY TUMOR VIRUS. The signaling pathway is initiated by the binding of WNT PROTEINS to cells surface WNT RECEPTORS which interact with the AXIN SIGNALING COMPLEX and an array of second messengers that influence the actions of BETA CATENIN.PyransRNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Polycomb Repressive Complex 1: A multisubunit polycomb protein complex with affinity for CHROMATIN that contains methylated HISTONE H3. It contains an E3 ubiquitin ligase activity that is specific for HISTONE H2A and works in conjunction with POLYCOMB REPRESSIVE COMPLEX 2 to effect EPIGENETIC REPRESSION.Epigenesis, Genetic: A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.Leukemia, Myeloid, Acute: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.Gene Rearrangement, B-Lymphocyte, Heavy Chain: Ordered rearrangement of B-lymphocyte variable gene regions of the IMMUNOGLOBULIN HEAVY CHAINS, thereby contributing to antibody diversity. It occurs during the first stage of differentiation of the IMMATURE B-LYMPHOCYTES.Genes, abl: Retrovirus-associated DNA sequences (abl) originally isolated from the Abelson murine leukemia virus (Ab-MuLV). The proto-oncogene abl (c-abl) codes for a protein that is a member of the tyrosine kinase family. The human c-abl gene is located at 9q34.1 on the long arm of chromosome 9. It is activated by translocation to bcr on chromosome 22 in chronic myelogenous leukemia.Recurrence: The return of a sign, symptom, or disease after a remission.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Tumor Burden: The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body.Survival Rate: 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.Glioma: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Directed Molecular Evolution: The techniques used to produce molecules exhibiting properties that conform to the demands of the experimenter. These techniques combine methods of generating structural changes with methods of selection. They are also used to examine proposed mechanisms of evolution under in vitro selection conditions.Wnt Proteins: Wnt proteins are a large family of secreted glycoproteins that play essential roles in EMBRYONIC AND FETAL DEVELOPMENT, and tissue maintenance. They bind to FRIZZLED RECEPTORS and act as PARACRINE PROTEIN FACTORS to initiate a variety of SIGNAL TRANSDUCTION PATHWAYS. The canonical Wnt signaling pathway stabilizes the transcriptional coactivator BETA CATENIN.Hedgehog Proteins: A family of intercellular signaling proteins that play and important role in regulating the development of many TISSUES and organs. Their name derives from the observation of a hedgehog-like appearance in DROSOPHILA embryos with genetic mutations that block their action.Mice, Inbred C57BLAntigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Liver Neoplasms: Tumors or cancer of the LIVER.Anemia, Aplastic: A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.Nestin: A type VI intermediate filament protein expressed mostly in nerve cells where it is associated with the survival, renewal and mitogen-stimulated proliferation of neural progenitor cells.Genetic Variation: Genotypic differences observed among individuals in a population.Cell Growth Processes: Processes required for CELL ENLARGEMENT and CELL PROLIFERATION.Drug Delivery Systems: Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Hematopoietic Stem Cell Mobilization: The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Colorectal Neoplasms: Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Mammary Glands, Human: Glandular tissue in the BREAST of human that is under the influence of hormones such as ESTROGENS; PROGESTINS; and PROLACTIN. In WOMEN, after PARTURITION, the mammary glands secrete milk (MILK, HUMAN) for the nourishment of the young.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Fusion Proteins, bcr-abl: Translation products of a fusion gene derived from CHROMOSOMAL TRANSLOCATION of C-ABL GENES to the genetic locus of the breakpoint cluster region gene on chromosome 22. Several different variants of the bcr-abl fusion proteins occur depending upon the precise location of the chromosomal breakpoint. These variants can be associated with distinct subtypes of leukemias such as PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; and NEUTROPHILIC LEUKEMIA, CHRONIC.Carcinoma, Squamous Cell: A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Cell Line: Established cell cultures that have the potential to propagate indefinitely.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Real-Time Polymerase Chain Reaction: Methods used for detecting the amplified DNA products from the polymerase chain reaction as they accumulate instead of at the end of the reaction.Stomach Neoplasms: Tumors or cancer of the STOMACH.Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell.Treatment Outcome: 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.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Carcinoma: A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)Neoplasm Recurrence, Local: The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site.Chromosomes, Human, Pair 8: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Adenocarcinoma: A malignant epithelial tumor with a glandular organization.Translocation, Genetic: A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.Cell Hypoxia: A condition of decreased oxygen content at the cellular level.Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Drug Screening Assays, Antitumor: Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.Veratrum Alkaloids: Alkaloids with powerful hypotensive effects isolated from American or European Hellebore (Veratrum viride Ait. Liliaceae and Veratrum album L. Liliaceae). They increase cholinergic and decrease adrenergic tone with appropriate side effects and at higher doses depress respiration and produce cardiac arrhythmias; only the ester alkaloids have been used as hypotensive agents in specific instances. They have been generally replaced by drugs with fewer adverse effects.Antineoplastic Combined Chemotherapy Protocols: 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.Antigens, CD34: Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Antigens, Thy-1: A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. Originally identified in the mouse, they are also found in other species including humans, and are expressed on brain neurons and other cells.Comparative Genomic Hybridization: A method for comparing two sets of chromosomal DNA by analyzing differences in the copy number and location of specific sequences. It is used to look for large sequence changes such as deletions, duplications, amplifications, or translocations.Twist Transcription Factor: A basic helix-loop-helix transcription factor that was originally identified in DROSOPHILA as essential for proper gastrulation and MESODERM formation. It plays an important role in EMBRYONIC DEVELOPMENT and CELL DIFFERENTIATION of MUSCLE CELLS, and is found in a wide variety of organisms.Regeneration: The physiological renewal, repair, or replacement of tissue.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Mice, Inbred BALB CEmbryonal Carcinoma Stem Cells: The malignant stem cells of TERATOCARCINOMAS, which resemble pluripotent stem cells of the BLASTOCYST INNER CELL MASS. The EC cells can be grown in vitro, and experimentally induced to differentiate. They are used as a model system for studying early embryonic cell differentiation.Mammary Neoplasms, Experimental: Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.Precursor B-Cell Lymphoblastic Leukemia-Lymphoma: A leukemia/lymphoma found predominately in children and adolescents and characterized by a high number of lymphoblasts and solid tumor lesions. Frequent sites involve LYMPH NODES, skin, and bones. It most commonly presents as leukemia.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.Niclosamide: An antihelmintic that is active against most tapeworms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p48)Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Triple Negative Breast Neoplasms: Breast neoplasms that do not express ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and do not overexpress the NEU RECEPTOR/HER-2 PROTO-ONCOGENE PROTEIN.Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).Myelodysplastic Syndromes: Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.Integrin alpha6: An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.Antigens, CD15: A trisaccharide antigen expressed on glycolipids and many cell-surface glycoproteins. In the blood the antigen is found on the surface of NEUTROPHILS; EOSINOPHILS; and MONOCYTES. In addition, CD15 antigen is a stage-specific embryonic antigen.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Transplantation, Autologous: Transplantation of an individual's own tissue from one site to another site.Proto-Oncogene Proteins c-kit: A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.Cell Aging: The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.

*Cancer stem cell

"Heterogeneity in Cancer: Cancer Stem Cells versus Clonal Evolution". Cell Press. 138 (5): 822-9. doi:10.1016/j.cell.2009.08.017 ... suggesting that any cell might become a cancer stem cell. In other words, a fully differentiated cell undergoes mutations or ... They examined cancer stem cell plasticity in which cancer stem cells can transition between non-cancer stem cells (Non-CSC) and ... "Evolution of the cancer stem cell model", Cell Stem Cell, 14 (3): 275-91, doi:10.1016/j.stem.2014.02.006, PMID 24607403 Barabé ...

*Stem cell

... when one stem cell develops into two differentiated daughter cells, another stem cell undergoes mitosis and produces two stem ... Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through ... "Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells". Nature. 197 ( ... Rakic, P (October 2009). "Evolution of the neocortex: a perspective from developmental biology". Nature Reviews. Neuroscience. ...

*Biological immortality

... and cell metabolism. Normal stem cells and germ cells can also be said to be immortal (when humans refer to the cell line).[ ... Among the most commonly used cell lines are HeLa and Jurkat, both of which are immortalized cancer cell lines. HeLa cells ... All hydra cells continually divide.[citation needed] It has been suggested that hydras do not undergo senescence, and, as such ... "individual animals in clonal lines of some planarian species replicating by fission have been maintained for over 15 years". ...

*Carcinogenesis

... termed Cancer Stem Cell. Cancer stem cells may arise from transformation of adult stem cells or differentiated cells within a ... Just like a population of animals undergoes evolution, an unchecked population of cells also can undergo evolution. This ... Cancer Hypotheses. 1 (1): 1-15. Nowell PC (October 1976). "The clonal evolution of tumor cell populations". Science. 194 (4260 ... Not all the cancer cells are dividing. Rather, a subset of the cells in a tumor, called cancer stem cells, replicate themselves ...

*Immunosenescence

Once matured and circulating throughout the peripheral system, T-cells still undergo deleterious age-dependent changes. ... Mocchegiani, E; M. Malavolta (2004). "NK and NKT cell functions in immunosenescence". Aging Cell. 3 (4): 177-184. doi:10.1111/j ... Hematopoietic stem cells (HSC), which provide the regulated lifelong supply of leukocyte progenitors that are in turn able to ... proliferation in response to antigenic stimulation the accumulation and the clonal expansion of memory and effector T-cells ...

*Somatic evolution in cancer

... cancer stem cells versus clonal evolution". Cell. 138 (5): 822-9. doi:10.1016/j.cell.2009.08.017. PMID 19737509. Bapat SA (June ... During the development of most cancers, primary tumor cells acquire the ability to undergo "invasion and metastasis" whereby ... The monoclonal model of cancer and the cancer stem-cell model are not mutually exclusive. Cancer stem cell arises by clonal ... The first malignant cell, that gives rise to the tumor, is often labeled a cancer stem cell. The cancer stem-cell hypothesis ...

*Large-cell lung carcinoma with rhabdoid phenotype

... "cancer stem cells" with epithelial characteristics or lineage. When viewed under a light microscope, the transformed cancer ... clonal evolution or a phenotypic mimic?". Hum. Pathol. 32 (10): 1102-8. doi:10.1053/hupa.2001.28252. PMID 11679945. Itakura E, ... is ubiquitous in rhabdoid cells. Co-expression of cytokeratins and vimentin are associated with cells undergoing epithelial- ... Chetty R (August 2000). "Combined large cell neuroendocrine, small cell and squamous carcinomas of the lung with rhabdoid cells ...

*Colorectal cancer

Khalek FJ, Gallicano GI, Mishra L (May 2010). "Colon Cancer Stem Cells". Gastrointest. Cancer Res. (Suppl 1): S16-S23. PMC ... This gene is associated with the proliferation, invasion and scattering of colon cancer cells in cell culture, and tumor growth ... In clinical studies, a pro-inflammatory response was found in patients with stage II-III colorectal cancer who underwent 2 ... Jans, Christoph; Meile, Leo; Lacroix, Christophe; Stevens, Marc J.A. (2015). "Genomics, evolution, and molecular epidemiology ...

*Immune system

... induces the target cell to undergo apoptosis. T cell killing of host cells is particularly important in preventing the ... B cells and T cells are the major types of lymphocytes and are derived from hematopoietic stem cells in the bone marrow. B ... Clearly, some tumors evade the immune system and go on to become cancers. Tumor cells often have a reduced number of MHC class ... rather than its cells. In the mid-1950s, Frank Burnet, inspired by a suggestion made by Niels Jerne, formulated the clonal ...

*Ageing

... cancer cells which have lost the ability to die when maintained in a cell culture such as the HeLa cell line, and specific stem ... Williams, George C. (1957). "Pleiotropy, Natural Selection, and the Evolution of Senescence". Evolution. 11 (4): 398-411. doi: ... Clonal immortality apart, there are certain species whose individual lifespans stand out among Earth's life-forms, including ... lifespan as inherently limited and makes a comparison with the innate immortality that a felled tree may have when undergoing ...

*Immunotherapy

Cell-based immunotherapies are effective for some cancers. Immune effector cells such as lymphocytes, macrophages, dendritic ... A variety of strategies are in use or are undergoing research and testing. Randomized controlled studies in different cancers ... "Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes". Science. 298 (5594): 850- ... "Preclinical ex vivo expansion of G-CSF-mobilized peripheral blood stem cells: effects of serum-free media, cytokine ...

*Mouse models of breast cancer metastasis

"Breast cancer stem cells-research opportunities utilizing mathematical modeling". Stem cell reviews. 3 (2): 176-82. doi:10.1007 ... "Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer". Cancer ... Lox recombination system Introduction of retro viral mutations Introduction of chemically induced mutations The mice undergoing ... Metastasis is a process of migration of tumour cells from the primary cancer site to a distant location where the cancer cells ...

*Tumor microenvironment

... in restricting T cell accumulation near cancer cells. Overcoming this restriction, combined with a T cell checkpoint antagonist ... "Bone Marrow-Derived Myofibroblasts Contribute to the Mesenchymal Stem Cell Niche and Promote Tumor Growth". Cancer Cell. 19 (2 ... While a lack of oxygen can cause glycolytic behavior in cells, tumor cells also undergo aerobic glycolysis, in which they ... while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells. The tumor ...

*X-inactivation

All mouse cells undergo an early, imprinted inactivation of the paternally-derived X chromosome in two-cell or four-cell stage ... Stanley Michael Gartler used X chromosome inactivation to demonstrate the clonal origin of cancers. Examining normal tissues ... In these modified stem cells, the Xist-mediated gene silencing seems to reverse some of the defects associated with Down's ... Connallon, Tim; Clark, Andrew G (2013). "Sex-Differential Selection and the Evolution of X Inactivation Strategies". ...

*Glossary of biology

... effector cell Plasma cells, also called plasma B cells, plasmocytes, plasmacytes, or effector B cells, are white blood cells ... chromosome A threadlike strand of DNA in the cell nucleus that carries the genes in a linear order. clonal selection . cloning ... This discipline includes fundamental research on the biochemistry, physiology, cell biology, ecology, evolution and clinical ... soil biology . soil microbiology . species . speciation . stem cell . steroid . structural biology The branch of molecular ...

*Neoplasm

A mutant or epigenetically altered stem cell may replace the other nearby stem cells by natural selection. Thus, a patch of ... Somatic evolution in cancer List of biological development disorders Epidemiology of cancer Birbrair A, Zhang T, Wang ZM, Messi ... These cells are presumed to be clonal - that is, they are derived from the same cell, and all carry the same genetic or ... Prior to the abnormal growth of tissue, as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or ...

*Plasma cell dyscrasia

... although one study suggests that the clonal plasma cells and clonal lymphocytes arise from a common hematological stem cell. In ... Plasma cells develop from B lymphocytes which are stimulated to undergo this maturational development by T lymphocytes during ... Repetition of such genetic changes underlie the evolution of a clinically silent plasma cell dyscrasia to an overt malignancy. ... that ordinarily controls cell growth adjacent to the normally highly active antibody gene promotor thereby creating a cancer- ...

*G&T-Seq

... this technique enables the study of clonal relationships and tumour evolution. As well, rare cell types and samples otherwise ... "The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells". Journal of molecular medicine ... The cDNA undergoes amplification using the universal primer (5'- AAGCAGTGGTATCAACGCAGAGT-3') for 18 cycles of PCR before it ... Xi-Xi Chen, Fan Bai (2015). "Single-cell analyses of circulating tumor cells". 癌症生物学与医学:英文版. 12 (3): 184-192. doi:10.7497/j. ...

*Fungus

Yang Y, Yang E, An Z, Liu X (May 2007). "Evolution of nematode-trapping cells of predatory fungi of the Orbiliaceae based on ... In contrast, similar-looking organisms, such as filamentous green algae, grow by repeated cell division within a chain of cells ... Fungi produce compounds that inhibit viruses and cancer cells. Specific metabolites, such as polysaccharide-K, ergotamine, and ... Money NP (October 2002). "Mushroom stem cells". BioEssays. 24 (10): 949-52. doi:10.1002/bies.10160. PMID 12325127. ...
Since the first evidence for cancer stem cells in leukemia, experimentalists have sought to identify tumorigenic subpopulations in solid tumors. In parallel, scientists have argued over the implications of the existence of this subpopulation. On one side, the cancer stem cell hypothesis posits that a small subset of cells within a tumor are responsible for tumorigenesis and are capable of recapitulating the entire tumor on their own. Under this hypothesis, a tumor may be conceptualized as a series of coupled compartments, representing populations of progressively differentiated cell types, starting from stem cells. The allure of this model is that it elegantly explains our therapeutic failures: we have been targeting the wrong cells. Alternatively, the ...
The gene, HER2, causes cancer stem cells to multiply and spread, explaining why HER2 has been linked to a more aggressive type of breast cancer and to metastatic disease, in which the cancer has spread beyond the breast, the researchers say.. Further, the drug Herceptin, which is used to treat HER2-positive breast cancer, was found to target and destroy the cancer stem cells. "This work suggests that the reason drugs that target HER2, such as Herceptin and Lapatanib, are so effective in breast cancer is that they target the cancer stem cell population. This finding provides further evidence for the cancer stem cell hypothesis," says study author Max S. Wicha, M.D., Distinguished Professor of Oncology and ...
Human Prostate Cancer Stem Cell Culture Extra-cellular Differentiation Matrix is essential for Differentiation of Human Prostate Cancer Stem Cell Cultures. This product requires Human Prostate Cancer Stem Cell Culture Media Cat#M36103-30 and Cells Cat# 36103-30. Also available Products ...
Accumulating experimental and clinical evidence indicated that breast cancer may arise from mammary stem/progenitor cells that posses the features like the ability of self-renewal and tumor generation from very few cells, slow cell division, differentiation into different lineages, selective resistance to radio- and chemo-therapy, constitutive activation of anti-apoptotic pathways and induction of angiogenesis, the ability to migrate and spread in metastasis. Many signaling pathways involved in regulation of normal mammary stem cells including Hedgehog, Bmi-1, Wnt, NOTCH, HER-2, p53 and PTEN/Akt/β-catenin pathways have been identified to play roles in breast cancer stem/progenitor cells. However, the involvement of estrogen signaling, a major signaling pathway in breast ...
Intratumor genetic heterogeneity is a key mechanism underlying tumor progression and therapeutic resistance. The prevailing model for explaining intratumor diversity, the clonal evolution model, has recently been challenged by proponents of the cancer stem cell hypothesis. To investigate this issue, we performed combined analyses of markers associated with cellular differentiation states and genotypic alterations in human breast carcinomas and evaluated diversity with ecological and evolutionary methods. Our analyses showed a high degree of genetic heterogeneity both within and between distinct tumor cell populations that were defined based on markers of cellular phenotypes including stem cell-like characteristics. In several tumors, stem cell-like and more-differentiated ...
TY - JOUR. T1 - Chemosensitization and inhibition of pancreatic cancer stem cell proliferation by overexpression of microRNA-205. AU - Chaudhary, Amit Kumar. AU - Mondal, Goutam. AU - Kumar, Virender. AU - Kattel, Krishna. AU - Mahato, Ram I. PY - 2017/8/28. Y1 - 2017/8/28. N2 - Treatment of pancreatic cancer with gemcitabine (GEM) is limited due to its rapid plasma metabolism and development of chemoresistance. MicroRNA (miRNA) regulates cancer stem cell (CSC) maintenance and induces chemoresistance in cancer cells. In this study, we observed differential downregulation of miR-205 (miR-205-5p) in human pancreatic cancer tissues and cells. Compared to GEM-sensitive MIA PaCa-2 cells, miR-205 was highly downregulated in GEM-resistant MIA PaCa-2R ...
Gene expression studies in Cancer provide an insight into the global functioning of tumor and their pathways. In our previous studies on Retinoblastoma tumors, using a two parameter analysis (size and phenotype), we observed a FSClo/SSClo population that was CD133-CD44+ CD90- and expressed primitive stem cell markers, lacking the expression of differentiation markers (Balla et al. 2009). Since, CD44 and CD90 expression was absent in Y79 cell line, we used CD133 to sort the cells and analysed for various stem cell assays. This study highlights gene expression signature specific to putative cancer stem cells in Y79 cell line.. ...
Neovascularization is required for solid tumor maintenance, progression, and metastasis. The most described contribution of cancer cells in tumor neovascularization is the secretion of factors, which attract various cell types to establish a microenvironment that promote blood vessel formation. The cancer stem cell hypothesis suggests that tumors are composed of cells that may share the differentiation capacity of normal stem cells. Similar to normal stem cells, cancer stem cells (CSCs) have the capacity to acquire different phenotypes. Thus, it is possible that CSCs have a bigger role in the process of tumor neovascularization. In this study, we show the capacity of a specific population of ...
The application of our prostate epithelium-specific Cre/loxP system to inactivate tumor suppressor genes had resulted in successful development of mouse models of prostate cancer. We further increased the efficiency of the conditional Pten deletion model of prostate adenocarcinoma by combining it with either a conditional luciferase or EGFP reporter line. The growth kinetics of the androgen dependent cancer (AD-Ca) and androgen-depletion independent recurrent cancer (ADI-Ca) could be followed non-invasively in live animals by bioluminescence imaging. We expect that such an investigation will be facilitated by timing the collection of tumorsat specific growth or re-growth points, an advantage that is provided by the model. The EGFP model can provide an opportunity to locate tumors or to isolate enriched populations of cancer cells from tumor tissues via fluorescence-based technologies. ...
In this report, we have identified a subpopulation of highly tumorigenic cancer cells within human pancreatic adenocarcinomas using a xenograft model in which primary human pancreatic adenocarcinoma cells were implanted in immunocompromised mice. These highly tumorigenic cancer cells were identified by expression of the cell surface markers CD44, CD24, and ESA. These cells displayed several features typically seen in stem cells, including the ability to both self-renew and generate differentiated progeny, the ability to differentiate to recapitulate the phenotype of the tumor from which they were derived, and activation of developmental signaling pathways.. We chose to examine expression of the markers CD44, CD24, and ESA based on studies in breast cancer, ...
Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic ...
Cancer stem cells (CSCs) possess high tumor-initiating capacity and have been reported to be resistant to therapeutics. Vice versa, therapy-resistant cancer cells seem to manifest CSC phenotypes and properties. It has been generally assumed that drug-resistant cancer cells may all be CSCs although the generality of this assumption is unknown. Here, we chronically treated Du145 prostate cancer cells with etoposide, paclitaxel and some experimental drugs (i.e., staurosporine and 2 paclitaxel analogs), which led to populations of drug-tolerant cells (DTCs). Surprisingly, these DTCs, when implanted either subcutaneously or orthotopically into NOD/SCID mice, exhibited much reduced tumorigenicity or were even non-tumorigenic. Drug-tolerant DLD1 colon ...
Cancer stem cells (CSCs) possess high tumor-initiating capacity and have been reported to be resistant to therapeutics. Vice versa, therapy-resistant cancer cells seem to manifest CSC phenotypes and properties. It has been generally assumed that drug-resistant cancer cells may all be CSCs although the generality of this assumption is unknown. Here, we chronically treated Du145 prostate cancer cells with etoposide, paclitaxel and some experimental drugs (i.e., staurosporine and 2 paclitaxel analogs), which led to populations of drug-tolerant cells (DTCs). Surprisingly, these DTCs, when implanted either subcutaneously or orthotopically into NOD/SCID mice, exhibited much reduced tumorigenicity or were even non-tumorigenic. Drug-tolerant DLD1 colon ...
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According to the clonal evolution model, tumour growth is driven by competing subclones in somatically evolving cancer cell populations, which gives rise to genetically heterogeneous tumours. Here we present a comparative targeted deep-sequencing approach combined with a customised statistical algorithm, called deepSNV, for detecting and quantifying subclonal single-nucleotide variants in mixed populations. We show in a rigorous experimental assessment that our approach is capable of detecting variants with frequencies as low as 1/10,000 alleles. In selected genomic loci of the TP53 and VHL genes isolated from matched tumour and normal samples of four renal cell carcinoma patients, we detect 24 variants at allele frequencies ranging from 0.0002 to 0.34. Moreover, we demonstrate how the allele frequencies of known single-nucleotide polymorphisms can be exploited to detect loss of heterozygosity. Our findings ...
Conceptual revolutions have taken place in the past ten years, which have dramatically changed the field of oncology. In particular, the vast array of cancer-type diseases has emerged. The immune system has been shown to play a central role in controlling pre-cancerous cells, leading to the emergence of new areas of research. Tumoral heterogeneity, the clonal architecture of cancer cell populations, cellular plasticity, and the increasingly strong arguments on the existence of cancer-initiating stem cells have led to a different perception of tumors, no longer as monolithic, uniform cell groups, but as changing ecosystems, sensitive to the surrounding conditions and selection pressure. Stratification of cancer by omic ...
Chris Miller is an Assistant Professor in the Division of Oncology and a member of the McDonnell Genome Institute. His focus is on developing and applying computational tools to provide insight into the origins and progression of cancer. Dr. Miller received Bachelor degrees in Biology and Computer Science from Truman State University. He received his PhD in Computational Biology from Baylor College of Medicine.. His core research interests include understanding the clonal architecture of tumors and how they evolve in response to therapy, with a special focus on hematologic cancers. His research also focuses on effective designing and targeting of cancer immunotherapies, developing open-source software for interpreting and visualizing genomic data, and integrative analysis that translates multi-dimensional genomic data into both functional and actionable contexts.. Dr. Millers Publications. Dr. Millers Website. ...
Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of ...
Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5,954 tumors to reveal and systematically validate 412 genetic interactions between germline polymorphisms and major somatic events, including tumor formation in specific tissues and alteration of specific cancer genes. Among germline-somatic interactions, we found germline variants in RBFOX1 that increased incidence of SF3B1 somatic mutation by 8-fold via functional alterations in RNA splicing. Similarly, 19p13.3 variants were associated with a 4-fold increased likelihood of somatic mutations in PTEN. In support of this association, we found that PTEN knockdown sensitizes the MTOR pathway to high expression of the 19p13.3 gene GNA11. Finally, we observed that stratifying patients by germline ...
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Author Summary Cancer is the consequence of an evolutionary process, which lasts several decades, is impossible to observe during most of its time, and only becomes apparent in late stages. We use mathematical modeling to shed light on the evolutionary dynamics of cancer by studying the accumulation of passenger mutations. We show that the frequencies obtained by passenger mutations depend strongly on the ratio of death and birth rates of cancer cells. We use genetic data of colorectal cancer to estimate this important quantity in vivo. We estimate the size of the cancer cell population that was present when a specific mutation first emerged. Our theory informs the analysis of cancer sequencing data and the phylogenetic reconstruction of cancer evolution.
In breast and pancreatic cancers, the majority of known mutational and copy number driver events are relatively early events [15],[16],[27],[29]. In ccRCC, however, the majority of identified driver mutations were found to be subclonal. In fact, inactivating mutations in the Von Hippel-Lindau tumor suppressor gene and loss of heterozygosity at chromosome 3p were the only somatic events occurring `early in ten ccRCC tumors analyzed [22]. Conversely, mutations in certain driver genes, including BAP1 (BRCA1 associated protein-1), PTEN (phosphatase and tensin homolog), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha), SETD2 (SET domain containing 2) and TP53 (encoding tumor protein p53), were always subclonal, and thus probably involved in ccRCC progression. Selection for mutations in these genes during later stages of ccRCC development is evidenced by the observation that different subclones acquire mutations in the same gene in ...
Supplementary Fig. S5 - Supplementary Fig. S5. Validation of redundant APC mutations. A, For one case (CRC2), two redundant APC mutations are validated by Sanger sequencing. One nonsense mutation (C,T; left) and one frameshift indel (AG,A; right) are shown for seven regional biopsies for the given case. For one primary case (CRC2-P1), the nonsense mutation is not observed, consistent with the metastasis-clonal presentation of this mutation. B, The copy number changes of the entire chromosome 5 are shown for seven regional biopsies. Entire loss of chromosome 5 is observed for CRC-P1. APC locus is incidated with a red dotted line ...
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The Tasmanian devil (Sarcophilus harrisii) is the worlds largest surviving marsupial carnivore. The devil facial tumour disease (DFTD) is currently threatening Tasmanian devils with extinction. Since its emergence around 1996, the disease has spread rapidly across the state resulting in a population decline of around 80 % [1]. This had led to Tasmanian devils being listed as endangered by the International Union for Conservation of Nature (IUCN) [2]. An unusual feature of DFTD is that it is transmitted as an allograft when Tasmanian devils bite each other [3, 4]. This makes DFTD one of only three naturally occurring clonally transmissible tumours along with canine transmissible venereal tumour in dogs [5], and a recently identified transmissible cancer in clams [6]. This tumour is able to transmit between unrelated hosts without eliciting an immune response [7, 8], but how this tumour avoids the host immune system is not fully understood. The tumour ...
In a recent post, Philip Gerlee highlighted the two biggest contributions of mathematical oncology to cancer research: (1) increasing focus on the progress of cancer as an evolutionary process, and (2) looking at the importance of tumor heterogeneity.. For the first point, the standard historical reference is: Nowell, P. C. (1976). The clonal evolution of tumor cell populations. Science, 194(4260): 23-28.. However, for the second point, although I am vaguely familiar with modern work, I dont know of a historical reference. When was tumour heterogeneity first recognized as important to cancer dynamics and treatment? Was this work related to mathematical or other modeling insights? If not, what is the first important mathematical (or computational) modeling work on tumour heterogeneity?. ...
Although childhood high hyperdiploid acute lymphoblastic leukemia is associated with a favorable outcome, 20% of patients still relapse. It is important to identify these patients already at diagnosis to ensure proper risk stratification. We have investigated 11 paired diagnostic and relapse samples with single nucleotide polymorphism array and mutation analyses of FLT3, KRAS, NRAS and PTPN11 in order to identify changes associated with relapse and to ascertain the genetic evolution patterns. Structural changes, mainly cryptic hemizygous deletions, were significantly more common at relapse (P,0.05). No single aberration was linked to relapse, but four deletions, involving IKZF1, PAX5, CDKN2A/B or AK3, were recurrent. On the basis of the genetic relationship between the paired samples, three groups were delineated: (1) identical genetic changes at diagnosis and relapse (2 of 11 cases), (2) clonal evolution with all changes at diagnosis being present at ...
Mantle cell lymphoma (MCL) is an aggressive tumor, but a subset of patients may follow an indolent clinical course. To understand the mechanisms underlying this biological heterogeneity, we performed whole-genome and/or whole-exome sequencing on 29 MCL cases and their respective matched normal DNA, as well as 6 MCL cell lines. Recurrently mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL patients. We identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the anti-apoptotic protein BIRC3 and Toll-like receptor 2 (TLR2); and the chromatin modifiers WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or subsequent MCL samples by whole-genome/whole-exome (n = 8) or targeted (n = 19) ...
Chromosomal instability (CIN) is a characteristic feature of cancer. In this review, we concentrate on mechanisms leading to CIN in myeloid neoplasia, i.e., myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The pathogenesis of myeloid neoplasia is complex and involves genetic and epigenetic alterations. Chromosome aberrations define specific subgroups and guide clinical decisions. Genomic instability may play an essential role in leukemogenesis by promoting the accumulation of genetic lesions responsible for clonal evolution. Indeed, disease progression is often driven by clonal evolution into complex karyotypes. Earlier studies have shown an association between telomere shortening and advanced MDS and underlined the important role of dysfunctional telomeres in the development of genetic instability and cancer. Several studies link chromosome rearrangements and aberrant DNA and histone ...
Note: This review is based upon a presentation at the 2013 American Society of Hematology (ASH) Annual Meeting, December 7-10 in New Orleans, Louisiana.The full abstract may be reviewed on the ASH Annual Meeting Web site. Search by entering the title in the search box. The abstract number is referenced to access the full report. Abstract # 802
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Tasmanian devils are breeding at younger ages, and researchers at the University of Tasmania in Australia believe the phenomenon is caused by an evolutionary response to the cancer that is devastating these small marsupials.. Devil facial tumor disease (DFTD) is a contagious form of cancer that has been infecting the animals since 1996.1 Tasmanian devils are carnivorous marsupials of the family Dasyuridae. These nocturnal predators are found exclusively on the island of Tasmania and are comprised of about 50 species. They have a normal life span of five to six years, usually breeding around the ages of two or three. However, since the disease is cutting their total years down to two or three, most females would ordinarily not live to rear their first litter.. Since the onset of the epidemic, Tasmanian devils have begun to breed as early as age one. "We could be seeing evolution occurring before our eyes. Watch this space!" zoologist Menna ...
It turns out that marsupials do not just make more genes for cathelicidin proteins, they also make more potent ones. Two cathelicidin proteins from the tammar wallaby (Macropus eugenii) were able to kill two different antibiotic-resistant bacteria (Klebsiella pneumoniae and Pseudomonas aeruginosa) [1].. A team of Australian researchers argued the Tasmanian devils may have an even greater need than wallabies for strong, broad-spectrum antimicrobials [1]. Offspring are born after only 30 days of gestation and weigh only 0.3 grams [1]. To get an idea of just how small this is, a paper clip weighs around 1 gram. Add to this highly altricial start the observation that Tasmanian devils lead a very aggressive lifestyle (they are not called devils for nothing), resulting in cuts and bites that require pathogen protection. If the calm tammar wallaby makes such potent proteins, what about the truculent Tasmanian devil?. To address this question, researchers Emma Peel and her colleagues began by searching ...
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A better understanding of P. infestans population dynamics will contribute to more durable disease management strategies, particularly if high-resolution neutral markers are combined with the use of functional markers, for example, for virulence toward individual R genes. Here, we analyzed the Dutch P. infestans population over an entire decade, determined the overall population structure, and described the emergence, dynamics, and displacement of the main clonal lineages in correlation with regional cultural practices.. STRUCTURE analysis using a set of 12 highly informative SSR markers splits the Dutch P. infestans population into three major clusters, which for Cluster 2, roughly corresponds to the NE geographical region of origin. Cluster 1 consists of a single clonal lineage, NL-001, with 27 subclones previously identified as genotype "Blue_13" (Lees et al. 2009). The subclonal lineages showed small but consistent differences, mostly by loss of alleles ...
The extent of intratumoral heterogeneity, the subclonal structures and the mechanisms of treatment-induced clonal selection by cisplatin was investigated in the squamous cell carcinoma cell line model FaDu. We picked 96 single cell-derived clones from the cisplatin-sensitive parental FaDu cell line. After expansion as separate cultures, these clones were tested for their sensitivity to CDDP. By this approach, we isolated individual cell clones that were primarily resistant (clones 5 & 78) and others that showed high sensitivity to CDDP (clones 46 & 54). Basal mRNA expression levels associated with CDDP sensitivity / resistance were determined in two independent microarray analyses.
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Cancer arises from accumulation of somatic mutations and accompanying evolutionary selection for growth advantage. During the evolutionary process, an ancestor clone branches into multiple clones, yielding intratumor heterogeneity. However, principles underlying intratumor heterogeneity have been poorly understood. Here, to explore the principles, we built a cellular automaton model, termed the BEP model, which can reproduce the branching cancer evolution in silico. We then extensively searched for conditions leading to high intratumor heterogeneity by performing simulations with various parameter settings on a supercomputer. Our result suggests that multiple driver genes of moderate strength can shape subclonal structures by positive natural selection. Moreover, we found that high mutation rate and a stem cell hierarchy can contribute to extremely high ...
TY - JOUR. T1 - Genetic heterogeneity in HER2 testing in breast cancer panel summary and guidelines. AU - Vance, Gail H.. AU - Barry, Todd S.. AU - Bloom, Kenneth J.. AU - Fitzgibbons, Patrick L.. AU - Hicks, David G.. AU - Jenkins, Robert B.. AU - Persons, Diane L.. AU - Tubbs, Raymond R.. AU - Hammond, M. Elizabeth H.. PY - 2009/4/1. Y1 - 2009/4/1. N2 - • Context.-Intratumoral heterogeneity of HER2 gene amplification has been well documented and represents subclonal diversity within the tumor. The reported incidence of intratumor HER2 amplification genetic heterogeneity ranges in the literature from approximately 5% to 30%. The presence of HER2 genetic heterogeneity may increase subjectivity in HER2 interpretation by the pathologist. Objectives.-To define HER2 genetic heterogeneity and to provide practice guidelines for examining and reporting breast tumors with genetic heterogeneity for improvement of HER2 testing in breast cancer. Design.-We convened an ...
Most PDTCs and ATCs are thought to arise from preexisting PTCs based on their frequent co-occurrence in the same tumor specimen, where they consistently share a driver mutation (36, 40). Our results, analyzed in the context of the PTC TCGA study, provide insights into tumor microevolution and lend support to this model of tumorigenesis. Particularly compelling in this regard is the fact that mutations in the TERT promoter, which are known to activate its transcription, display a stepwise increase in frequency along the spectrum of disease progression (9% in PTCs, 40% in PDTCs, and 73% in ATCs) (1, 17-20). Interestingly, TERT mutations are subclonal in the few PTCs that harbor them, whereas they are clonal in PDTCs and ATCs, pointing to selection during tumor evolution, possibly by inducing cell immortalization. TERT promoter mutations also track with virulence of advanced disease. They are significantly associated with BRAF ...
Background: PIK3CA is the single most commonly mutated gene in breast cancer, with highest incidence reported in ER positive and HER2 negative breast cancer. Substantial data now suggests that breast cancers show intra-tumoural genetic heterogeneity, with apparently clonal tumours composed of multiple populations of tumour cells that, in addition to the founder genetic events common to all cells, harbour private genetic alterations. Tumours with mutations that are sub-clonal may respond less well to therapies targeting these mutations than cancers with clonal mutations. To assess how frequently PIK3CA mutations are clonal founder mutations, or may be subclonal, we assessed the abundance on PIK3CA mutation using digital PCR.. Methods: DNA was extracted from frozen sections of 119 primary ...
A Single-Cell Atlas of the Tumor and Immune Ecosystem of Human Breast Cancer Tumors displayed individuality in tumor cell composition, including phenotypic abnormalities and phenotype dominance. Relationship analyses between tumor and immune cells revealed characteristics of ecosystems related to immunosuppression and poor prognosis. [Cell] Full Article , Press Release , Graphical Abstract Resistance to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Mediated by a Reversible Drug-Tolerant State Barcode-mediated clonal tracking and genomic sequencing of patient-derived xenograft tumors revealed that residual tumors remaining after treatment with standard frontline chemotherapies, doxorubicin combined with cyclophosphamide, maintained the subclonal architecture of untreated tumors, yet their transcriptomes, ...
The management of advanced colorectal cancer uses combination systemic chemotherapy with 5-fluorouracil (5-FU), irinotecan, and oxaliplatin. The EGFR-targeted agents cetuximab and panitumumab are important additions to the treatment of colorectal cancer and have demonstrated survival benefits in randomized controlled trials. However, patients cumulative exposure to drug therapy is high, with the associated toxicities and financial costs.. The concept that tumors are heterogeneous both within a single tumor lesion and between tumor lesions in the same patient (intratumor heterogeneity) has become well established over the last 30 years (1, 2). As tumors consist of diverse subclonal populations with differing genomes, epigenomes, transcriptomes, and proteomes related through a common progenitor, the capacity to evolve and develop resistance in response to selective pressures such as prolonged exposure to targeted therapies presents a ...
The ALK tyrosine kinase receptor is oncogenically activated in neuroblastoma. Whereas numerous ALK fusion genes have been reported in different malignancies, in neuroblastoma ALK is mainly activated through point mutations. Three hotspot residues (F1174, F1245, and R1275) account for 85% of mutant ALK seen in neuroblastoma. In a cohort of 105 Swedish neuroblastoma cases of all stages, these hotspot regions were re-sequenced (> 5000X). ALK mutations were detected in 16 of 105 patients (range of variant allele fraction: 2.7-60%). Mutations at the F1174 and F1245 hotspot were observed in eleven and three cases respectively. ALK mutations were also detected at the I1171 and L1240 codons in one tumor each. No mutations were detected at R1275. Sanger sequencing could confirm ALK status for all mutated samples with variant allele fraction above 15%. Four of the samples with subclonal ALK mutation fraction below this would have gone undetected relying on Sanger sequencing only. No distinct mutation ...
Brady, Samuel W., Jasmine A. McQuerry, Yi Qiao, Stephen R. Piccolo, Gajendra Shrestha, David F. Jenkins, Ryan M. Layer, et al. 2017. "Combating Subclonal Evolution of Resistant Cancer Phenotypes." Nature Communications 8 (1): 883. 10.1038/s41467-017-01174-3. Goldberg, Lisa R., Stacey L. Kirkpatrick, Neema Yazdani, Kimberly P. Luttik, Olga A. Lacki, R. Keith Babbs, David F. Jenkins, W. Evan Johnson, and Camron D. Bryant. 2017. "Casein Kinase 1-Epsilon Deletion Increases Mu Opioid Receptor-Dependent Behaviors and Binge Eating." Genes, Brain, and Behavior, June. 10.1111/gbb.12397. Rahman, Mumtahena†, Shelley M. MacNeil†, David F. Jenkins†, Gajendra Shrestha, Sydney R. Wyatt, Jasmine A. McQuerry, Stephen R. Piccolo, Laura M. Heiser, Joe W. Gray, W. Evan Johnson and Andrea H. Bild. 2017. "Activity of Distinct Growth Factor Receptor Network Components in Breast Tumors Uncovers Two Biologically Relevant Subtypes." Genome Medicine 9 (1): 40. ...
... s were so named for their crabby, aggressive behavior (especially around food and mating time) and the absolutely bizarre sounds that they make. They are solitary, non-monogamous, nocturnal animals, and live in burrows. Devils eat a wide variety of other creatures, though they typically only hunt things that are smaller than themselves. They also consume carrion, and thanks to their powerful teeth and jaws, are able to completely consume an animal. Devils are at their most aggressive when feeding, as it is a time that the normally solitary creatures come together and (attempt to) share a meal ...
The outcome of patients with MM has improved substantially during the last decades as a result of drug development and progress in the understanding of disease biology.11,12 However, even in the era of novel agents some patients with high-risk cytogenetic abnormalities or early relapse after first-line treatment have a dismal outcome.13,14 Clonal heterogeneity and evolution are contributors to disease progression and ultimately refractoriness in MM.6 So far, there are only limited data available that proved clonal evolution in patients relapsing after ASCT for newly diagnosed disease. With our current analysis of 128 patients with FISH data at primary diagnosis and relapse after ASCT we demonstrate that high-risk cytogenetic abnormalities occur more frequently at relapse. This observation was especially due to de novo gains of chromosome 1q and new deletions of chromosome 17p. No changes were observed between primary diagnosis and relapse ...
Multistage carcinogenesis is an evolutionary process in which genetic instability generates new clones and natural selection among such variants drives clonal expansions (1, 2, 3, 4, 5, 6) . The number of genetic lesions necessary to produce a cancer is unknown for most tissues but has been variously estimated to be 2 to 12 (7, 8, 9) . Normal mutation rates in the absence of clonal expansion cannot account for the accumulation of so many lesions (10) . There has been much debate in the literature as to the relative importance of a mutator phenotype (10 , 11) and genetic instability (3 , 12) versus clonal expansion (4 , 5) in neoplastic progression.. Both genetic instability and clonal expansions are commonly observed in neoplastic progression, and it is likely that the two factors cooperate in clonal evolution (11 , 13) . If this is true, then expansion of a genetically ...
Neuroblastoma, a clinically heterogeneous pediatric cancer, is characterized by distinct genomic profiles but few recurrent mutations. As neuroblastoma is expected to have high degree of genetic heterogeneity, study of neuroblastomas clonal evolution with deep coverage whole-genome sequencing of diagnosis and relapse samples will lead to a better understanding of the molecular events associated with relapse. Samples were included in this study if sufficient DNA from constitutional, diagnosis and relapse tumors was available for WGS. Whole genome sequencing was performed on trios (constitutional, diagnose and relapse DNA) from eight patients using Illumina Hi-seq2500 leading to paired-ends (PE) 90x90 for 6 of them and 100x100 for two. Expected coverage for sample NB0175 100x100bp was 30X for tumor and constitutional samples. For the seven other patients expected coverage was 80X for tumor samples with PE 100x100, 100X in the other tumor samples and 50X for ...
A week or so ago, Ann Maree Pearce, a government cytogeneticist from Australias island state, Tasmania, and colleagues said in a Nature news report that a nasty facial cancer affecting the Tasmanian devil population, dubbed Devil Facial Tumour Disease, was in fact an infective cell line being passed between the ferocious, foxed-sized scavengers via bites and so on. At the linkurl:18th Lorne Cancer Conference Erskine on the Beach;http://www.the-scientist.com/blog/display/23110/ in Lorne, Austra
Cancers can be categorized into two groups: those whose frequency increases with age, and those resulting from errors during mammalian development. The first group is linked to DNA replication through the accumulation of genetic mutations that occur during proliferation of developmentally acquired stem cells that give rise to and maintain tissues and organs. These mutations, which result from DNA replication errors as well as environmental insults, fall into two categories; cancer driver mutations that initiate carcinogenesis and genome destabilizing mutations that promote aneuploidy through excess genome duplication and chromatid missegregation. Increased genome instability results in accelerated clonal evolution leading to the appearance of more aggressive clones with increased drug resistance. The second group of cancers, termed germ cell neoplasia, ...
Since cancer shares the same molecular machinery as the host, most therapeutic interventions which aim to target cancer would inadvertently also adversely affect the host. Additionally, cancer continuously evolves, streamlining its host-derived genome for a new single-celled existence. In particular, short-term clinical success observed with most antineoplastic therapies directly relate to the fact that cancer is constantly evolving. However, the clonal evolution of cancer occasionally also render cancer cells uniquely susceptible to therapeutic interventions, as is exemplified by the clinical relevance of synthetic lethality. Synthetic lethality describes a situation where the simultaneous loss of function in two genes results in lethality, but where a loss of function in either single gene is tolerated. This observation ...
Study Throws Light on Mutations Facilitating Cancer Cell Survival Next generation sequencing (NGS) is becoming increasingly integrated into oncological practice and clinical research. NGS methods have also provided evidence for clonal evolution of cancers during disease progression and treatment. Now, with the help of this sophisticated sequencing method, researchers identified genetic mutations that promote the […]. The post Study Throws Light on Mutations Facilitating Cancer Cell Survival appeared first on BioTecNika .Read more at www.biotecnika.org/2018/03/study-throws-light-on-mutations-facilitating-cancer-cell-survival/. ...
WES of patient-matched tumor pairs from 23 individuals with HNSCC demonstrates the intertumor genetic heterogeneity of this cancer. To our knowledge, this is the first study of HNSCC to examine intertumor genetic heterogeneity in synchronous nodal metastases and metachronous recurrence across multiple patients; it provides a model to determine patterns of mutation and clonal evolution that may be targetable for the treatment of recurrent/metastatic disease.. Primary tumors in our study averaged 67.6 nonsynonymous SSNVs per tumor, including mutations in tumor suppressor genes, oncogenes, and genes that have previously been found to be significantly mutated in HNSCC, such as AJUBA, CASP8, FAT1, FBXW7, NFE2L2, and TP53 (Supplemental Table 10 and Supplemental Table 4). Interestingly, primary tumors were not found to harbor mutations in several tumor suppressor genes and oncogenes previously implicated in HNSCC, including CCND1, PIK3CA, NOTCH1, PTEN, CDKN2A, ...
Advances in hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) have improved survival in severe aplastic anemia (SAA) from 10%-20% in the 1960s to 80%-90% today. A matched sibling HSCT is the treatment of choice in younger patients, whereas IST is often used in older patients or in those who lack a histocompatible sibling. Graft rejection, GVHD, and poor immune reconstitution (with associated infectious complications) limit the success of HSCT, whereas lack of response, relapse, and clonal evolution limit the success of IST.
The liver CSC concept has been acknowledged to explain the molecular diversity of malignant phenotypes in liver cancer. However, many questions remain, including the role of hepatitis viruses, the origin of liver CSCs, the existence and role of the stem cell niche, similarities and differences between normal hepatic stem/progenitor cells and liver CSCs, the timing of CSC emergence, CSC concept universality in liver cancers, and the relationship between CSC plasticity and clonal evolution accompanied by genetic and epigenetic changes (11). Although chronic HBV and HCV infections are two major risk factors for the development of liver cancer, their roles in liver CSCs are largely unknown. It is also unclear whether HBV and HCV infect and replicate in hepatic stem/progenitor cells, but a recent ...
Urothelial carcinomas are frequently multicentric, occurring at multiple separate sites within the urinary tract (4, 5). Urothelial tumor multifocality is often present before the onset of clinical symptoms (3), and patients with multiple, separate tumors are at higher risk for recurrence, progression, and cancer-related death (4, 5, 44). Although numerous studies have been done to address the clonal nature of multifocal urothelial carcinoma, no consensus currently exists on whether these lesions are monoclonal in origin or whether they arise independently. Two explanations have been proposed to explain tumor multifocality within the urothelium: the monoclonal theory and the "field-effect" theory. Whereas the two theories are not mutually exclusive, it is unknown which mechanism is more important in leading to urothelial tumor multifocality. Detailed characterization and comparison of genetic alterations in the ...
Considerable progress has been made in the treatment of multiple myeloma in the past decade with median survival for the disease improving significantly. This has come through a combination of better understanding of the disease biology and coordinated research into new treatment approaches including better supportive care. However, patients eventually become refractory to available treatments and succumb to the disease, highlighting the need to develop new treatment approaches. The genetic heterogeneity in the disease and clonal evolution under treatment pressure underlie the development of resistance, underscoring the need to develop more effective therapies that can eradicate the disease at initial treatment as well as the need for new classes of drugs with varying mechanisms of action ...
Notably, the average size of persisting clones increased linearly with time, and their size distribution acquired long-term scaling behavior, a hallmark of a single functionally equivalent population of cells dividing at the same rate (Fig. 2C and fig. S6, A, B, and E) (18-21). Studies of interfollicular epidermis (IFE) revealed that this pattern of clonal evolution was consistent with progenitors dividing stochastically to generate differentiated and cycling daughters with equal probability (18, 19). By implementing a Bayesian inference analysis, we showed that the entire data set conforms to the IFE paradigm (Fig. 2E; fig. S6, C to E; and supplementary theory). We conclude that esophageal progenitors (EP) are functionally equivalent.. The observation of similar progenitor behavior in EE and epidermis, derived from endoderm and ectoderm, respectively, argues that squamous epithelia share a common mechanism of homeostasis irrespective of ...
As a growing body of evidence demonstrates intertumoral and intratumoral heterogeneity and clonal evolution, both during carcinogenesis and also throughout treatment resulting in acquired drug resistance, the utility of blood-based assays or "liquid biopsies" is becoming increasingly recognized in clinical practice and trial design. "Liquid biopsies" provide a less invasive approach to the current gold standard of interrogating tumors by tissue biopsies, which are frequently unfeasible, associated with morbidity, and cannot be performed as often ...
Using quantitative clonal strategies, we confirmed that RSCs are located at the peripheral extremity of the CMZ, which functions as a stem cell niche (Raymond et al., 2006; Xue and Harris, 2012), where they divide mainly in the radial orientation promoting asymmetric fate outcome and ensuring a constant production of RPCs. We also show that the same simple model (using the same parameters) that was shown to describe the clonal evolution in embryonic RPCs (He et al., 2012) fits the proliferative statistics of RPCs in the CMZ, suggesting the functional equivalency of the embryonic and CMZ progenitor cells.. The location of RSCs at the extreme periphery of the CMZ is consistent with previous studies based on molecular markers and label retention (Ahmad et al., 2004; Johns, 1977; Ohnuma et al., 2002; Xue and Harris, 2012). The position of RSCs in the CMZ, with access to the apical epithelial ...
Correction: The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research Nat Prod Rep. 2019 01 01; 36(1):248-249. . View in PubMed. The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research Nat Prod Rep. 2019 01 01; 36(1):35-107. . View in PubMed. Rare Pediatric Invasive Gliofibroma Has BRAFV600E Mutation and Transiently Responds to Targeted Therapy Before Progressive Clonal Evolution JCO Precis Oncol. 2019; 3. . View in PubMed. Noninvasive estimation of fetal lung maturity with magnetic resonance spectroscopy Am J Obstet Gynecol. 2018 08; 219(2):209-210. . View in PubMed. Association between Subcortical Morphology and Cerebral White Matter Energy Metabolism in Neonates with Congenital Heart Disease Sci Rep. 2018 09 19; 8(1):14057. . View in PubMed. Clinical Factors Associated with Cerebral Metabolism in Term Neonates with Congenital Heart ...
The devil is apparently in the chromosomes.. In 1996 there were approximately 250,000 Tasmanian devils (Sarcophilus harrisii) in the wild, but by 2009 their numbers had crashed to less than 50,000 - some populations decreased by 90 per cent. The cause: the infamous Devil Facial Tumour Disease (DFTD), a transmissible cancer that has now decimated 85 per cent of Tasmanian devils in the wild.. It is estimated that over 100,000 animals have died from this unsightly disease and, despite all our hopes, its not showing any signs of slowing down. In fact, new research from the University of Sydney (USYD) suggests that this disease is able to survive indefinitely and could possibly get stronger in the future.. These hopes werent completely unfounded, the disease has been out there among the devils for 16 years and has divided millions of times, according to USYD postdoctoral research fellow Beata Ujvari. The low genetic material allows the disease to spread between individuals - its one of only three ...
Australian scientists said on Thursday they had made a breakthrough in the fight to save the cancer-hit Tasmanian devil by mapping the species genome for the first time.
Tasmanian devils have highly complex and ancient immunoglobulin light chain variable repertoires. Our article with Kathy Belov just gone online. Check out: http://www.sciencedirect.com/science/article/pii/S0165242715001750
Lachish, S and Jones, ME and McCallum, HI (2007) The impact of disease on the survival and population growth rate of the Tasmanian devil. Journal of Animal Ecology, 76. pp. 926-936. ISSN 0021-8790 ...
Researchers believe the milk of the Tasmanian devil can hold the key to fighting drug-resistant bacteria. This milk builds a strong immune system that protects the joeys from infection and pathogens.
The Tasmanian devil, another iconic animal of Tasmania, is now the islands largest surviving carnivorous marsupial. It is known for its powerful jaws and scream-like vocalizations. Tasmanian devils are also unique because they suffer from devil facial tumor disease - an infectious, non-viral parasitic cancer which they can transmit to one another through fighting. While the unusual disease makes the animals of interest to cancer researchers, it is threatening the survival of the remaining Tasmanian devils, whose wild population has declined by 70 percent during the past 20 years ...
In the same way, the Thorny Devil "sucks up" water. So, if the Thorny Devil wants a drink, it can simply step in water and suck up the entire puddle and bring the water to its mouth with the tiny channels on its skin. It never even has to put its mouth in the water. This ability keeps the lizard alive, because any dew or moisture on plants or in the sand can be taken into its body this way.. Also, God gave the Thorny Devil several interesting ways to defend itself. Of course, the most obvious defensive tool of the Thorny Devil is its spiky skin. Just think, if you were a predator, would you want to eat something that looks like a pincushion, full of sharp spikes? Me neither. In addition to its spikes, the Thorny Devil has a "false head" on its neck just behind his real head. This false head is large and spiky. When the Thorny Devil is threatened, it can lower its real head between its front two legs and raise its "false head" to look like a head. By doing this, it protects its vital, important ...
Definition of blue devil in the online dictionary, Lexipedia. The meaning of blue devil. What does blue devil mean? blue devil synonyms, blue devil antonyms. Information about blue devil in the free online dictionary and thesaurus.
Here are some very clear clips for the immune responses to infection, starting with a really well done explanation of Burnets Nobel-winning clonal selection theory: If you like that, check out some more of the videos from the Walter and Eliza Hall Institute of Medical Research. Try this animation and quiz: McGraw Hill Online Centre…
The Ope Ope no Mi is a Paramecia-type Devil Fruit that allows its user to create a the effect will result as a normal cut, as seen when the SAD gushed out of the . Despite the ROOM being stationary, in both One Piece: Gigant Battle 2 and Missing: leathers. The Artificial Devil Fruit is a type of Devil Fruit created by scientific means, as he was barely big enough to carry Monkey D. Luffy, a normal-sized human. A few Missing: leathers. Im talking about experience here as a anime fan, not a One Piece fan. I know that there can only be one devil fruit at a time but has Oda actually said and it doesnt prove how grammatically correct it is, but it certainly rolls off the tongue better. . I think they onky became standard because of laws on health and safety nd ...
The Tasmanian Devil is afflicted by a unique type of contagious cancer that s never been seen in nature before Unless the spread of the cancer can be stopped the Devils could be wiped out with devas
Something extraordinary is evolving among the feisty inhabitants of the remote north-west coast of Tasmania. Something thats both astounding and delighting the researchers monitoring them. For more than 20 years, these apple-isle locals have been suffering an ugly cancer thats caused population numbers to rapidly decline. The problem has raised many complex questions and stirred urgent…
Shop all Dirt Devil products - Choose from a huge selection of Dirt Devil products from the most popular online stores at BHG.com Shop.
In this paper we present a new kind of vortex lenses in which the radial phase distribution is characterized by the "devils staircase" function. The focusing properties of these fractal DOEs coined Devils vortex-lenses are analytically studied and the influence of the topological charge is investigated. It is shown that under monochromatic illumination a vortex devils lens give rise a focal volume containing a delimited chain of vortices that are axially distributed according to the self-similarity of the lens.. ©2009 Optical Society of America. Full Article , PDF Article ...
Lyrics to Heart Of The Devil by Danzig: I am / Heart / Of the devil / I have / Heart / Of the / Devil / I can make a man / Freeze in his
A unique approach to connecting people and ideas in the life sciences, creating a space for probing conversations and deep insight into the topics and trends shaping our future.
The former chief of Eli Lilly USA is picked to replace Tom Price, who stepped down in September amid a controversy over the abuse of taxpayer-funded travel.. 0 Comments. ...
Buy Natures Way Devils Claw Standardized - 480 mg - 90 Capsules at the lowest price from eVitamins. Find Devils Claw Standardized reviews, side effects, coupons and more from eVitamins.
Devil Fruits Devil Fruits are mystical fruits found in the world that can give the eater many different and varying kinds of strange and interesting abilities,
The Devil You Know has 4,171 ratings and 145 reviews. Julie (jjmachshev) said: Whew! Im almost at a loss for words. The Devil You Know is book 2 in Je...
Lennie Roberts, the original protagonist for the Devils Slide tunnel, drills the symbolic first hole as excavation begins on the south portal of the Devils Slide Tunnel, which will speed the trip from San Francisco to Half Moon Bay ...
The cancer, which causes genital tumors in dogs and is spread by sexual contact, is 11,000 years old. By Marc Silver National Geographic Canines are in a rare category when it comes to cancer: They and Tasmanian devils are the only two animals that can transmit it from one individual to another. A new genetic study…
Brock Lesnar: The champ erased any doubt about the legitimacy of his title reign when he methodically pounded out former conqueror Mir in two rounds at UFC 100 back in July. Lesnars game plan, which he executed masterfully, showed his tremendous improvement as a fighter since the first time the pair squared off. Rather than come out like an angry Tasmanian Devil with instant takedowns and wild ground-and-pound attacks, the champ executed a takedown, expertly moved into side control during the transition, took his time to make sure that he had the proper position, and then unloaded the most devastating series of arm punches in UFC history in a way that left him wholly unexposed to submission attempts or sweeps. It was as dominant of a performance as we have seen in the heavyweight division in quite a long time. Now that Lesnar is back in training following his bout with that pesky little bacteria, he finally has what appears to be a clear number one contender in undefeated Mexican-American ...
The Tasmanian Department of Primary Industries, Parks, Water and Environment (DPIPWE) is seeking comments on the strategies, objectives and recovery actions outlined in the Draft Tasmanian Devil Recovery Plan. Comments must be received by 11 February 2011. read more... ...
Devils Pact: Less than Perfect. Kyburi was disappointed that she hadnt been able to rattle Agura to the point where shed be reduced to a quivering wreck - her life would have been so much easier if that had happened. Those sorts were more willing to give up their secrets than the Human female, whom she had a sort of respect for. There were few beings in the Multiverse that could have the mentality of an icicle when they where inches from death at her claws, not counting the other members of the Red Sentient 5, and even fewer of those had the audacity to insult her under such circumstances. Agura was one of those beings.. The point remained - the Red Sentient female had no intention of fighting Agura down here, where the rock jammed her comm. and positioning devices, making it impossible to alert Krytus of her position. Better to do it aboveground, where the RS5 could join her in subduing the driver of the green, inferior vehicle that was so similar to the Venikus.. Green. Sun and stars, why ...
Get your own copy of this Blue-Ray Movie at SwapaDVD.com. If youre not yet a member, your first DVD and membership are free! All you have to do is post 10 DVDs you want to get rid of. Visit the site to find a huge selection of movies!
Ilya Kovalchuk will not play for the Devils in either game of a home-and-home set against the Capitals this weekend, NorthJersey.com reports. Kovalchuk has not...
Tony Scott made a short film called Beat the Devil. Hes gone, but he left us this interesting film to remember him by. It stars James Brown, Clive Owen, Gary Oldman and Marilyn Manson. ...
... Basic Rules Any member can roll for a fruit, no matter what kind of progress was made. Members can be just starting out and still be able to tr
With the new NHL season quickly approaching, I figured it was time to look at the New Jersey Devils historical stats against every team in the league...
The Devils celebrate following a second-period goal by defenseman Anton Volchenkov (not pictured) that was deflected into the net off Kings defenseman Slava Voynov (not pictured) during Game 1 of the Stanley Cup Final.
Cowpokes on Devils Thumb Ranch | We didnt forget our little wranglers. All childrens treatments are booked in a couples treatment room with a parent…
PVP Tienda: 7.95€ / P.V.P Web: 7.55€ Serie: Defense Devil Autor: Youn In-Wan / Yang Kyung-Il Editorial: Panini Páginas: 206 páginas B/N Idioma: Castellano 
He hopes to remain with the New Jersey Devils long-term, he said. The fact that he is playing on a one-year contract had more do with circumstances than calculation.
人之初3性本善》性相近3习相远》 苟不教3性乃迁》教之道3贵以专》 昔孟母3择邻处》子不学3断机杼》 窦燕山3有义方》教五子3名俱扬》 养不教3父之过》教不严3师之惰》 子不学3非所宜》幼不学3老何为》 玉不琢3不成器》人不学3不知义》 为人子3方少时》亲师友3习礼仪》 香九龄3能温席》孝于亲3所当执》 融四岁3能让梨》弟于长3宜先知》 首孝弟3次见闻》知某数3识某文》 一而十3十而百》百而千3千而万》 三才者3天地人》三光者3日月星》 三纲者3君臣义》父子亲3夫妇顺》 曰春夏3曰秋冬》此四时3运不穷》 曰南北3曰西东》此四方3应乎中》 曰水火3木金土》此五行3本乎数》 十干者3甲至癸》十二支3子至亥》 曰黄道3日所躔》曰赤道3当中权》 赤道下3温暖极》我中华3在东北》 ...
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Cancer stem cell metabolism | Breast Cancer Research | Full TextCancer stem cell metabolism | Breast Cancer Research | Full Text

... are not mutually exclusive and can be viewed as integrated processes because CSCs can themselves undergo clonal evolution, ... The cancer stem cell model: Omnis cellula e cellula Adult stem cells, in contrast to most cells in our body, which are ... Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells ... Aguilar-Gallardo C, Simon C. Cells, stem cells, and cancer stem cells. Semin Reprod Med. 2013;31(1):5-13.View ArticlePubMed ...
more infohttps://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-016-0712-6

Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall | Cancer Cell...Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall | Cancer Cell...

CD133-positive cells, isolated from the tumor, expressed stem cell markers including nestin, CD133, Ki67, Sox2, EFNB1, EFNB2, ... CD133-positive cancer stem cells, which are likely the driving force for the rapid recurrence of the tumor in the patient. ... Ex vivo organotypic brain slice co-culture showed that the CD133+ cells behaved like tumor cells. The CD133-positive cells also ... Expression of unique cancer-related transcripts in these CD133-positive cells, such as caveolin-1 and −2, do not appear to have ...
more infohttps://cancerci.biomedcentral.com/articles/10.1186/1475-2867-12-41

Cancers  | Free Full-Text | Epigenetics, Nervous System Tumors, and Cancer Stem Cells | HTMLCancers | Free Full-Text | Epigenetics, Nervous System Tumors, and Cancer Stem Cells | HTML

... highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells ( ... We believe that better understanding how epigenetic mechanisms operate in neural cells and identifying the etiologies and ... one of the hallmarks of cancer. In this review, we describe the major epigenetic mechanisms (i.e., DNA methylation, histone and ... consequences of epigenetic deregulation in tumor cells and CSCs, in particular, are likely to promote the development of ...
more infohttp://www.mdpi.com/2072-6694/3/3/3525/htm

March | 2015 | microrna inhibitorMarch | 2015 | microrna inhibitor

Furnari and colleagues showed that CSCs undergo clonal evolution from just one GBM cancer stem cell to intensive heterogeneity ... ACSVL3 loss of perform promotes cancer stem cell differentiation and inhibits tumor initiation properties of cancer stem cells ... colorectal and breast cancer cell lines. Meanwhile, colorectal and breast cancer cell lines too as ordinary human fibroblast ... a smaller molecule inhibitor of ACSVL3 could inhibit the development of GBM stem cells too as non stem tumor cells. While there ...
more infohttps://micrornainhibitor.com/2015/03

Cancer stem cell - WikipediaCancer stem cell - Wikipedia

"Heterogeneity in Cancer: Cancer Stem Cells versus Clonal Evolution". Cell Press. 138 (5): 822-9. doi:10.1016/j.cell.2009.08.017 ... suggesting that any cell might become a cancer stem cell. In other words, a fully differentiated cell undergoes mutations or ... They examined cancer stem cell plasticity in which cancer stem cells can transition between non-cancer stem cells (Non-CSC) and ... "Evolution of the cancer stem cell model", Cell Stem Cell, 14 (3): 275-91, doi:10.1016/j.stem.2014.02.006, PMID 24607403 Barabé ...
more infohttps://en.wikipedia.org/wiki/Cancer_stem_cell

Somatic evolution in cancer - WikipediaSomatic evolution in cancer - Wikipedia

"Heterogeneity in cancer: cancer stem cells versus clonal evolution". Cell. 138 (5): 822-9. doi:10.1016/j.cell.2009.08.017 ... During the development of most cancers, primary tumor cells acquire the ability to undergo "invasion and metastasis" whereby ... The monoclonal model of cancer and the cancer stem-cell model are not mutually exclusive.[90] Cancer stem cell arises by clonal ... Cancer stem cells[edit]. Main article: Cancer stem cell. The first malignant cell, that gives rise to the tumor, is often ...
more infohttps://en.wikipedia.org/wiki/Somatic_evolution_in_cancer

Canonical and non-canonical WNT signaling in cancer stem cells and their niches: Cellular heterogeneity, omics reprogramming,...Canonical and non-canonical WNT signaling in cancer stem cells and their niches: Cellular heterogeneity, omics reprogramming,...

Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. Cancer Discov. 7:264-276. ... Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic ... Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal ... The cancer stem cell niche: How essential is the niche in regulating stemness of tumor cells? Cell Stem Cell. 16:225-238. 2015 ...
more infohttps://spandidos-publications.com/ijo/51/5/1357

Colorectal Cancer Biomarkers and the Potential Role of Cancer Stem CellsColorectal Cancer Biomarkers and the Potential Role of Cancer Stem Cells

... the theory of clonal evolution was introduced by Nowell in 1976 stating, 1. A number of external or internal stem cell insults ... Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division. Stem Cells. ... The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell stem cell. 2011;8 ... Colorectal cancer stem cells. Stem Cells. 2012;30:363-71 57. Subramaniam D, Ramalingam S, Houchen CW, Anant S. Cancer stem ...
more infohttp://www.jcancer.org/v04p0241.htm

Gene expression in murine mammary epithelial stem cell-like cells shows similarities to human breast cancer gene expression |...Gene expression in murine mammary epithelial stem cell-like cells shows similarities to human breast cancer gene expression |...

To determine a possible association between mammary stem cells and breast cancer, a detailed characterization of the ... transcriptome in mammary stem cells is essential. We have used a murine mammary epithelial stem-like cell line (HC11) and made ... in a breast cancer perspective provide a unique map of the transcriptomic changes and a number of novel mammary stem cell ... Subsequently, we have performed a cross-species comparison to reveal conserved gene expression between stem cells and subtype- ...
more infohttps://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr2256

Oncolytic adenoviruses targeted to cancer stem cells | Molecular Cancer TherapeuticsOncolytic adenoviruses targeted to cancer stem cells | Molecular Cancer Therapeutics

Historic models of cancer cell propagation have been explained by the "clonal evolution" model and the "stochastic" model. The ... Given their clonal nature, cancer cells undergo processes similar to the self-renewal and differentiation of normal stem cells ... Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem ... Stem cells, cancer, and cancer stem cells. Nature 2001;414:105-11. ...
more infohttp://mct.aacrjournals.org/content/8/8/2096

Iterative sorting reveals CD133+ and CD133- melanoma cells as phenotypically distinct populations | BMC Cancer | Full TextIterative sorting reveals CD133+ and CD133- melanoma cells as phenotypically distinct populations | BMC Cancer | Full Text

... with CD133 considered to be a cancer stem cell marker in melanoma as well as other tumours, but its role has remained ... and that these two populations have distinct characteristics not related to the cancer stem cell phenotype. In vitro, gene set ... Loss of CD133 from the surface of a CD133+ cell was observed in vitro and in vivo, however CD133- cells derived from CD133+ ... We iteratively sorted CD133+ and CD133- cells from 3 metastatic melanoma cell lines, and observed tumourigenicity and ...
more infohttps://0-bmccancer-biomedcentral-com.brum.beds.ac.uk/articles/10.1186/s12885-016-2759-2

Glioblastoma Stem Cell Clonal Dynamics Drive Intratumor Heterogeneity | Cancer DiscoveryGlioblastoma Stem Cell Clonal Dynamics Drive Intratumor Heterogeneity | Cancer Discovery

... which then undergo symmetric division to produce either progenitor cells or nondividing cells that rapidly undergo apoptosis. ... Approach: GBM stem cell clonal evolution was assessed by lentiviral barcoding of primary GBM. ... GBM stem cells (GSC), the radioresistant and chemoresistant CD133+ stem-like cell subpopulation of GBMs, has been shown to ... Glioblastoma Stem Cell Clonal Dynamics Drive Intratumor Heterogeneity Message Subject (Your Name) has forwarded a page to you ...
more infohttp://cancerdiscovery.aacrjournals.org/content/early/2017/09/15/2159-8290.CD-RW2017-172.full

Ockhams razor for the MET-driven invasive growth linking idiopathic pulmonary fibrosis and cancer | Journal of Translational...Ockham's razor for the MET-driven invasive growth linking idiopathic pulmonary fibrosis and cancer | Journal of Translational...

... as well as cooperating in the evolution of cancer metastasis when aberrantly activated. Growing evidence sustains that MET ... Receptor tyrosine kinases (RTK) are known to be key players in cancer onset and progression. It has been demonstrated that RTK ... Holland JD, Klaus A, Garrat AN, Birchmeier W. Wnt signaling in stem and cancer stem cells. Curr Opin Cell Biol. 2013;25(2):254- ... MET, a driver of invasive growth and cancer clonal evolution under therapeutic pressure. Curr Opin Cell Biol. 2014;31:98-105. ...
more infohttps://translational-medicine.biomedcentral.com/articles/10.1186/s12967-016-1008-4

Researchers find genetic precursors of leukemia in patients treated for non-blood cancersResearchers find genetic precursors of leukemia in patients treated for non-blood cancers

In a study of nearly 9,000 people treated for solid tumor cancers, researchers found that radiation treatment and tobacco use ... The study, published in the journal Cell Stem Cell, revealed new risk factors for "clonal hematopoiesis," a medical phenomenon ... A significant percentage of lymphoma patients undergoing transplants with their own blood stem cells carry acquired genetic ... CLL evolution under the microscope. August 11, 2017 How do initially benign forms of cancer evolve to become aggressive? In a ...
more infohttps://medicalxpress.com/news/2017-08-genetic-precursors-leukemia-patients-non-blood.html

Evolutionary trajectory of leukemic clones and its clinical implications | HaematologicaEvolutionary trajectory of leukemic clones and its clinical implications | Haematologica

... when patients that undergo allogeneic stem cell transplantation develop an AML that originates in the donor hematopoietic cells ... VAF threshold as well as a documentation of clonal temporal evolution (by having at least two assessments of the clonal ... Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014;371(26):2477-2487. ... Concise review: age-related clonal hematopoiesis: stem cells tempting the devil. Stem Cells. 2018;36(9):1287-1294. ...
more infohttp://www.haematologica.org/node/80476.full.print

Grant Finder | Leukemia and Lymphoma SocietyGrant Finder | Leukemia and Lymphoma Society

We take the T cells from the blood of the original stem cell donor, grow them in the laboratory and train the cells so that ... When a cell has accumulated excess DNA damage it is recognized by the cell machinery and makes the cell undergo permanent ... Chemotherapy, which poisons fast-dividing cancer cells, also induces senescence in many normal cells. If these damaged cells ... Additionally, the same technology will be applied to study the development and evolution of single cells in a leukemia model in ...
more infohttps://www.lls.org/grant-finder?page=8

Considering Clonality in Precision Medicine - The ASCO PostConsidering Clonality in Precision Medicine - The ASCO Post

Furthermore, tumor initiator clones (also often referred to as cancer stem cells) have been identified in a subset of cancers ... This means that all daughter cells that evolve following this initial event (ie, every cell in the clonal pool) also carry the ... Clonal evolution and clonal dominance will be important considerations in precision medicine as an increasing repertoire of ... When Can Patients With Gleason 6 Prostate Cancer Safely Undergo Active Surveillance?. ASCO and ASH Release Update to Clinical ...
more infohttps://ascopost.com/issues/june-25-2015/considering-clonality-in-precision-medicine/

JoVE | Peer Reviewed Scientific Video Journal - Methods and ProtocolsJoVE | Peer Reviewed Scientific Video Journal - Methods and Protocols

Understanding and targeting these cancer stem cells in breast cancer, which may possess enhanced chemo- and radio-resistance ... Inhibitors of cell death result in decreased release of 51Cr. As effector cells, we used an activated autoreactive clonal ... This could render b3a2 CML cells more prone to aneuploidy and clonal evolution than b2a2 progenitors and may therefore explain ... In contrast, non-CSCs were not eliminated by metformin treatment, but rather underwent reversible cell cycle arrest. Therefore ...
more infohttps://www.jove.com/visualize/abstract/26087013/clonal-evolution-blast-crisis-correlate-with-enhanced-proteolytic

JCI -
Cancer stem cells in the development of liver cancerJCI - Cancer stem cells in the development of liver cancer

The clonal evolution of tumor cell populations. Science. 1976;194(4260):23-28.. View this article via: PubMed CrossRef Google ... liver CSCs co-expressing CD44 were detected in all HCC tissues from 13 HCC patients who underwent surgery (20). These cells ... Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell. 2008;13(2):153-166.. View this article via: PubMed ... of cancer as an abnormal stem cell disease was proposed based on the similar capabilities of cancer cells and normal stem cells ...
more infohttps://www.jci.org/articles/view/66024

Mouse Clone Model for evaluating the immunogenicity and tumorigenicity of pluripotent stem cells | Stem Cell Research &..."Mouse Clone Model" for evaluating the immunogenicity and tumorigenicity of pluripotent stem cells | Stem Cell Research &...

To investigate the immune-rejection and tumor-formation potentials of induced pluripotent stem cells and other stem cells, we ... some stem cells can accumulate to form tumors when they undergo clonal evolution [25, 26]. Using the "Mouse Clone Model" for ... Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105-11. ... for the investigation of stem cell therapy. ESC Embryonic stem cell, ICM Inner cell mass, iPSC Induced pluripotent stem cell ...
more infohttps://stemcellres.biomedcentral.com/articles/10.1186/s13287-015-0262-3

The impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML | Blood JournalThe impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML | Blood Journal

Chronic myelogenous leukemia (CML) is a clonal hematopoietic stem cell disorder characterized by a specific chromosomal ... A study at MD Anderson Cancer Center concluded that the prognostic significance of clonal evolution in CML is not uniform and ... no cells positive for the Ph chromosome), partial (1%-35% of cells Ph positive), minor (36%-65% of cells Ph positive), and ... Patients were followed up every 2 weeks for the first 8 weeks for clinical assessment and underwent bone marrow evaluations, ...
more infohttp://www.bloodjournal.org/content/100/5/1628?ijkey=9d119106c2be7a828e5b7ecd0e1cc2b9caa948db&keytype2=tf_ipsecsha&sso-checked=true

An Epigenetic Reprogramming Strategy to Resensitize Radioresistant Prostate Cancer Cells | Cancer ResearchAn Epigenetic Reprogramming Strategy to Resensitize Radioresistant Prostate Cancer Cells | Cancer Research

Evolution of the cancer stem cell model. Cell Stem Cell 2014;14:275-91. ... this is the first study demonstrating that radioresistant cell populations within prostate cancer cells undergo a phenotypic ... Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 2012;481:506-10. ... EZH2 protects glioma stem cells from radiation-induced cell death in a MELK/FOXM1-dependent manner. Stem Cell Rep 2015;4:226-38 ...
more infohttp://cancerres.aacrjournals.org/content/76/9/2637

Italian Ministry of HealthItalian Ministry of Health

Replication stress response in cancer stem cells as a target for chemotherapy. Research output: Contribution to journal › ... Oral management of adult patients undergoing hematopoietic stem cell transplantation. Research output: Contribution to journal ... Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma. Research output: ... CHK1-targeted therapy to deplete DNA replication-stressed, p53-deficient, hyperdiploid colorectal cancer stem cells. Research ...
more infohttps://moh-it.pure.elsevier.com/en/projects/e68dc04d-23b2-4dbe-a3a3-517dad51ab42

Contribution of the Microenvironmental Niche to Glioblastoma HeterogeneityContribution of the Microenvironmental Niche to Glioblastoma Heterogeneity

J. Mathieu, Z. Zhang, W. Zhou et al., "HIF induces human embryonic stem cell markers in cancer cells," Cancer Research, vol. 71 ... Clonal evolution hypothesis suggests that most cancers arise from a single altered cell which facilitates tumor initiation and ... as the proneural cells undergo transformation to mesenchymal subtype. Downregulation of proneural-specific markers and ... J. D. Lathia, J. Gallagher, J. M. Heddleston et al., "Integrin alpha 6 regulates glioblastoma stem cells," Cell Stem Cell, vol ...
more infohttps://www.hindawi.com/journals/bmri/2017/9634172/

Starter Grants for Clinical Lecturers | The Academy of Medical SciencesStarter Grants for Clinical Lecturers | The Academy of Medical Sciences

Yin Wu, University College London, Investigating the immune regulation of non-small cell lung cancer by gamma-delta T-cells ... Laura Jardine, Newcastle University, The evolution of clonal haematopoiesis in individuals with heterozygous GATA2 mutation ... Single cell transcriptome profiling of mutant haematopoietic stem and progenitor cells (HSPCs) in patients with ... Analysis of cellular immune function in patients with Chronic Lymphocytic Leukaemia who are undergoing therapy with novel ...
more infohttps://acmedsci.ac.uk/grants-and-schemes/grant-schemes/starter-grants
  • In 1976, Peter C. Nowell, MD , proposed a model of clonal evolution in Science magazine in which he suggested "tumor progression results from acquired genetic variability within the original clone allowing sequential selection of more aggressive sublines. (ascopost.com)
  • Comparison of the temozolomide-treated xenografts with untreated xenografts showed that although most of the cells were temozolomide-sensitive and exhibited nonexponential growth, temozolomide-resistant clones and a small subset of pretreatment clones did not exhibit nonexponential growth. (aacrjournals.org)
  • Of the subset of patients they actively followed, those with clonal hematopoiesis had a small - 1 percent - but increased, estimated incidence of developing blood cancer later on. (medicalxpress.com)
  • This model suggests that only certain subpopulations of cancer stem cells have the ability to drive the progression of cancer, meaning that there are specific (intrinsic) characteristics that can be identified and then targeted to destroy a tumor long-term without the need to battle the whole tumor. (wikipedia.org)
  • Therefore, we hypothesized that CRC stem cell markers (CRCSC) can identify a group of patients whom are at increased risk for recurrence or progression of disease. (jcancer.org)
  • To characterize the clonal dynamics of GSCs at different stages of malignant progression, Lan and colleagues performed serial orthotopic implantations of mice with primary and recurrent human GBM cells transduced with a lentiviral barcode library and treated the mice with either temozolomide or vehicle in the second and third passages of xenograft. (aacrjournals.org)
  • Receptor tyrosine kinases (RTK) are known to be key players in cancer onset and progression. (biomedcentral.com)
  • The reality is that we do not currently have a good understanding of SC numbers, their division frequencies for most human tissues, and the diversity of cell types or environmental perturbations that can initiate cancer and lead to progression. (aacrjournals.org)
  • We show for the first time the necessity of iterative sorting to isolate pure marker-positive and marker-negative populations for comparative studies, and present evidence that despite CD133+ and CD133- cells being equally tumourigenic, they display distinct phenotypic differences, suggesting CD133 may define a distinct lineage in melanoma. (beds.ac.uk)
  • This concept is further supported by lineage tracing and clonal analysis experiments that demonstrate the hierarchical organization of tumor in vivo [ 12 - 14 ]. (hindawi.com)
  • In addition, recent reports add more complexity to this scenario by demonstrating that cancer cells have a remarkable degree of plasticity. (biomedcentral.com)
  • This pathway-called the PI3K-mTOR pathway-is hyperactive in most human cancers (including leukemia, lymphoma, and myeloma) and it controls the uptake and flow of nutrients through cancer cells. (lls.org)
  • Twenty-five percent of the patients in the study had clonal hematopoiesis. (medicalxpress.com)
  • The presence of clonal hematopoiesis can lead to an increased risk for subsequent blood cancers ," said UNC Lineberger's Catherine Coombs, MD. "We wouldn't recommend forgoing treatment that is medically indicated because the risk of a secondary cancer is relatively low, but it is important to closely watch those patients who are high-risk. (medicalxpress.com)
  • Clonal hematopoiesis was also strongly associated with current or former tobacco use. (medicalxpress.com)
  • A major risk factor for developing clonal hematopoiesis that can be modified or changed is tobacco use," Coombs said. (medicalxpress.com)
  • However, for patients who did get a blood cancer, the risk was higher for patients who had clonal hematopoiesis. (medicalxpress.com)
  • Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes, Cell Stem Cell (2017). (medicalxpress.com)
  • These cells inhibit normal hematopoiesis resulting in BM failure. (haematologica.org)
  • In contrast, a related treatment with the Imatinib Mesylate order parental UROtsa cells or their transformed coun terparts together with the demethylating agent, 5 AZC, had no effect about the expression of MT 3 mRNA over that of untreated cells. (micrornainhibitor.com)
  • In vitro, gene set enrichment analysis indicated CD133+ cells were related to a proliferative phenotype, whereas CD133- cells were of an invasive phenotype. (beds.ac.uk)
  • Loss of CD133 from the surface of a CD133+ cell was observed in vitro and in vivo, however CD133- cells derived from CD133+ retained the CD133+ phenotype, even in the presence of signals from the tumour microenvironment. (beds.ac.uk)
  • Histological examination of the tumor established it as being a high-grade glial neoplasm, characterized by polygonal and fusiform cells with marked nuclear atypia, amphophilic cytoplasm, prominent nucleoli, frequent mitotic figures, irregular zones of necrosis and vascular hyperplasia. (biomedcentral.com)
  • In this way, a population of mutant cells, called a clone, can expand in the neoplasm. (wikipedia.org)
  • Oral mucosa SC estimates (head and neck squamous cell carcinoma) reference HSC and murine intestinal SC studies (their Supplementary references 39 and 65). (aacrjournals.org)
  • Moreover, newly arising ACA under imatinib treatment and clonal evolution are considered features of acceleration and define failure of therapy according to the European LeukemiaNet (ELN) recommendations. (jove.com)
  • Once patients have other signs of acceleration, clonal evolution predicts lower response rates and a shorter time to treatment failure. (bloodjournal.org)
  • The theory suggests that conventional chemotherapies kill differentiated or differentiating cells, which form the bulk of the tumor but do not generate new cells. (wikipedia.org)
  • However, despite its widespread role in human cancer, we still only vaguely understand how PI3K-mTOR signaling drives tumor metabolism and consequently, there are only a handful of general therapeutic strategies to target it in development. (lls.org)
  • There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. (biomedcentral.com)
  • Precision cancer medicine entails treating patients based upon the molecular characteristics of their tumor. (ascopost.com)
  • Modern descriptions of biological evolution will typically elaborate on major contributing factors to evolution such as the formation of local micro-environments, mutational robustness, molecular degeneracy , and cryptic genetic variation. (wikipedia.org)
  • This physiological genetic program supports embryonic development and post-natal organ regeneration, as well as cooperating in the evolution of cancer metastasis when aberrantly activated. (biomedcentral.com)
  • The study analyzed genetic changes from 8,810 MSK cancer patients. (medicalxpress.com)
  • As we approach the 40th anniversary of this theory and stand upon the doorstep of being able to therapeutically target acquired genetic alterations in a variety of diseases, this concept of clonal evolution becomes increasingly important. (ascopost.com)
  • The dismal prognosis is largely attributed to the heterogeneous nature of the tumor, which in addition to intrinsic molecular and genetic changes is also influenced by the microenvironmental niche in which the glioma cells reside. (hindawi.com)
  • Cancer stem cells were first identified by John Dick in acute myeloid leukemia in the late 1990s. (wikipedia.org)
  • The aim of this review is to shed light upon recent observations in leukemia evolution and their clinical implications. (haematologica.org)
  • Acute myeloid leukemia (AML) is a clonal disorder that originates in leukemic stem and progenitor cells, termed blasts. (haematologica.org)
  • The discovery of BCR/ABL as a driver oncogene in chronic myeloid leukemia (CML) resulted in the development of Imatinib, which, in fact, demonstrated the potential of targeting the kinase in cancers by effectively treating the CML patients. (jove.com)
  • Chronic myelogenous leukemia (CML) is a clonal hematopoietic stem cell disorder characterized by a specific chromosomal translocation, t(9;22), resulting in a shortened chromosome 22, commonly referred to as the Philadelphia (Ph) chromosome. (bloodjournal.org)
  • This report shed shadows on the great promise of iPSCs as the renewable sources of autologous cells for regenerative medicine. (biomedcentral.com)
  • Since these early ventures into the use of oncolytic viruses, much has been discovered about the biology of cancer and the understanding of developing efficacious antitumor therapies. (aacrjournals.org)
  • A deeper understanding of this critical interface between signaling and metabolism would have broad impact in cancer biology. (lls.org)