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.Neoplastic Stem Cells: Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.Colony-Forming Units Assay: A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.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.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.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.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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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)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)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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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.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.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.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Adult Stem Cells: Cells with high proliferative and self renewal capacities derived from adults.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.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.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.Pluripotent Stem Cells: Cells that can give rise to cells of the three different GERM LAYERS.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.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.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.Stem Cell Niche: A particular zone of tissue composed of a specialized microenvironment where stem cells are retained in a undifferentiated, self-renewable state.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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.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.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.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Induced Pluripotent Stem Cells: Cells from adult organisms that have been reprogrammed into a pluripotential state similar to that of EMBRYONIC STEM CELLS.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.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.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.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.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)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).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.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.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.

*  Neurosphere Assays: Growth Factors and Hormone Differences in Tumor and Nontumor Studies - Chaichana - 2006 - STEM CELLS -...

Neurosphere assays are the standard for studying these stem-like cells in both normal and cancer tissues. Despite the ... This self-renewing capacity also makes these neural stem cells a possible source of brain tumors, which was supported by the ... Adult Neural Stem Cells From the Subventricular Zone: A Review of the Neurosphere Assay, The Anatomical Record, 2013, 296, 9, ... dogma that the brain is quiescent throughout adult life has been challenged by the discovery of cells with stem cell-like ...

*  'leukemia t cell' Protocols and Video...

Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting', 'Systematic Analysis of In Vitro Cell Rolling ... Transplantation of Zebrafish Pediatric Brain Tumors into Immune-competent Hosts for Long-term Study of Tumor Cell Behavior and ... Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines', 'Clinical Application of Sleeping Beauty and ... Quantifying the Frequency of Tumor-propagating Cells Using Limiting Dilution Cell Transplantation in Syngeneic Zebrafish', ' ...

*  'eukaryotic initiation factor 5' Protocols and Video...

Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting', 'Analysis of RNA Processing Reactions Using ... Retroviral Infection of Murine Embryonic Stem Cell Derived Embryoid Body Cells for Analysis of Hematopoietic Differentiation ... In Vitro Transcription Assays and Their Application in Drug Discovery', 'Analysis of Termination of Transcription Using BrUTP- ... Sealable Femtoliter Chamber Arrays for Cell-free Biology', 'Investigating the Function of Coronin A in the Early Starvation ...

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

Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting ... Developmental Biology, Issue 56, CD133, liver stem cell, oval cell, liver cancer stem cell, stem cell, cell isolation, non- ... Only a relatively small fraction of cells in the tumor with stem cell properties, termed brain tumor initiating cells (BTICs), ... Various cell types could be analyzed using this technique, including lymphocytes/leukocytes, stem cells, and tumor cells. ...

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

Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting ... Developmental Biology, Issue 56, CD133, liver stem cell, oval cell, liver cancer stem cell, stem cell, cell isolation, non- ... Only a relatively small fraction of cells in the tumor with stem cell properties, termed brain tumor initiating cells (BTICs), ... Medicine, Issue 85, Cancer Stem Cells, Tumor Initiating Cells, Prostate Cancer, HLA class I, Primary Prostate Cancer, ...

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

Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting ... Only a relatively small fraction of cells in the tumor with stem cell properties, termed brain tumor initiating cells (BTICs), ... Various cell types could be analyzed using this technique, including lymphocytes/leukocytes, stem cells, and tumor cells. ... We found that some tumor cell lines such as melanoma B16F1 cells, glioblastoma U87 cells, and breast cancer MDA-MB-435 cells ...

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

Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting ... Developmental Biology, Issue 56, CD133, liver stem cell, oval cell, liver cancer stem cell, stem cell, cell isolation, non- ... Only a relatively small fraction of cells in the tumor with stem cell properties, termed brain tumor initiating cells (BTICs), ... Stem Cell Biology, Issue 91, Induced pluripotent stem cells; reprogramming; intermediates; fluorescent activated cells sorting ...

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

Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting ... Only a relatively small fraction of cells in the tumor with stem cell properties, termed brain tumor initiating cells (BTICs), ... Cancer Biology, Issue 67, Stem Cell Biology, Medicine, Cellular Biology, Molecular Biology, BTIC (brain tumor initiating cells ... However, using HIV-1 infected primary T-cells as target cells in NK cell functional assays has been difficult due the presence ...

*  Predicting Tumor Responses to Mitomycin C on the Basis of DT-Diaphorase Activity or Drug Metabolism by Tumor Homogenates:...

Selby P. J., Buick R. N., Tannock I. A critical appraisal of the human tumor stem cell assay. N. Engl. J. Med., 308: 129-134, ... Tumor homogenates were washed twice with PBS, passed through sieves (200-50 μm), and viable tumor cells were counted. The assay ... Hamburger A. W., Salmon S. E. Primary bioassay of human tumor stem cells. Science (Washington DC), 197: 461-463, 1977. ... to DTD activity measurements were also tested for their response to MMC treatment in the tumor stem cell/clonogenic assay in ...

*  Anti-Prostate Stem Cell Antigen Monoclonal Antibody 1G8 Induces Cell Death In vitro and Inhibits Tumor Growth In vivo via a Fc...

Cell Killing Assays. LNCaP-PSCA cells (1.5 × 105-4 × 105) were cultured in triplicate in six-well plates in RPMI 1640 ... Anti-Prostate Stem Cell Antigen Monoclonal Antibody 1G8 Induces Cell Death In vitro and Inhibits Tumor Growth In vivo via a Fc- ... Anti-Prostate Stem Cell Antigen Monoclonal Antibody 1G8 Induces Cell Death In vitro and Inhibits Tumor Growth In vivo via a Fc- ... Anti-Prostate Stem Cell Antigen Monoclonal Antibody 1G8 Induces Cell Death In vitro and Inhibits Tumor Growth In vivo via a Fc- ...

*  In Vivo Programming of Tumor Antigen-Specific T Lymphocytes from Pluripotent Stem Cells to Promote Cancer Immunosurveillance |...

D, in vivo proliferation/cytotoxicity assay. CFSEhi (right peaks) and CFSElo (left peaks) target cells were pulsed with OVA257- ... ACT and tumor challenge. A total of 3 × 106 GFP+ DsRed+ iPS cells or bone marrow-derived CD117+ Lin− hematopoietic stem cells ( ... G7 tumor cells. A, Ag-specific T-cell persistence. Seven weeks post tumor challenge or 13 weeks without tumor challenge, CD8+ V ... tumor tissues were examined for tumor-reactive T-cell infiltration. A, H&E staining. Inflammatory cells infiltrated in tumor ...

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

Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting ... Only a relatively small fraction of cells in the tumor with stem cell properties, termed brain tumor initiating cells (BTICs), ... Stem Cell Biology, Issue 91, Induced pluripotent stem cells; reprogramming; intermediates; fluorescent activated cells sorting ... Cell Alignment, Heart Progenitors, in vitro Differentiation, Transgenic Mice, Mouse Embryonic Stem Cells, stem cells, ...

*  'stem cell factor' Protocols and Video...

Isolation of CD133+ Liver Stem Cells for Clonal Expansion', 'Processing of Primary Brain Tumor Tissue for Stem Cell Assays and ... In vitro Enrichment of Ovarian Cancer Tumor-initiating Cells', 'Pluripotent Stem Cell Derived Cardiac Cells for Myocardial ... A cGMP-applicable Expansion Method for Aggregates of Human Neural Stem and Progenitor Cells Derived From Pluripotent Stem Cells ... Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data ...

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

... mechanisms operate in neural cells and identifying the etiologies and consequences of epigenetic deregulation in tumor cells ... which are thought to be present in a range of nervous system tumors and responsible for tumor maintenance, progression, ... highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells ( ... and discuss the broad spectrum of epigenetic alterations that have been uncovered in pediatric and adult nervous system tumors ...

*  Cancer stem cells in multiple myeloma

Mouse myeloma tumor stem cells: a primary cell culture assay. J. Natl. Cancer Inst. 1971;46:411-422. [PubMed] ... and CD138neg cells in vitro suggesting that they are active against both mature tumor cells and cancer stem cells [73]. ... engrafting tumor cells consisted of both CD38hi plasma cells as well as CD19+ B cells, but the capacity of each of these cell ... Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem ...

*  In vitro chemotherapy testing (Larry Weisenthal)

Human tumor stem cell assay. New Eng J Med 308:1478-79, 1983). In my laboratory, we throw away the single cells and attempt to ... tumor cells give rise to immortalized cell lines have a very poor prognosis, > relative to patients whose tumor cells do not ... tumor-infiltrating effector cells. The DISC assay is the only assay reported to be capable of distinguishing between specific ... have used true fresh tumor assays and not short-term cell lines. Yet the NCI applied this technology to cell lines and Shaw ...

*  Unraveling tumor growth one stem cell at a time | EurekAlert! Science News

... suspected to have a stem cell origin as they advance our understanding of how single stem cells are subverted to cause tumors. ... that a single mutation in a leukemia-associated gene reduces the ability of blood stem cells to make more blood stem cells, but ... leaves their progeny daughter cells unaffected. Their findings have relevance to all cancers that are ... "Combining mathematical modeling with a large number of single stem cell assays allowed us to predict which cells lose their ...

*  Leukemia - The Mll-Een knockin fusion gene enhances proliferation of myeloid progenitors derived from mouse embryonic stem...

105 cells plated in each round of the self-renewal assay. ES, embryonic stem cell, EBs, embryoid bodies; SCF, stem cell factor ... 42 and as an adaptor protein can act as tumour suppressor in rat fibroblast Ras transformation assays.. 43 In vitro studies on ... ES cells were maintained as stem cells on mitomycin C inactivated feeder layer. At 48 h before differentiation, the ES cells ... HOXB4-induced expansion of adult hematopoietic stem cells ex vivo. Cell 2002; 109: 39-45. , Article , PubMed , ISI , ChemPort , ...

*  FORUM of CLINICAL ONCOLOGY Quarterly official publication of the Hellenic Society of Medical Oncology - PDF

Tumour stem cells: the relevance of predictive assays for tumour control after radiotherapy. Radiother Oncol 1994 Jan; 30(1): ... In addition, local recurrence could be the result of tumour regrowth of within the initial tumour bed; or of tumour in the same ... the number of cells surviving after RT, is: N = N 0 x S. Given that a tumour is controlled when every single clonogenic cell ... Consequently, hypofractionation in breast cancer may have a reasonable radiobiological background as more tumour cells will be ...

*  Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML | Blood Journal

ddC also targeted leukemic stem cells in secondary AML xenotransplantation assays. Thus, AML cells have increased cytidine ... In animal models of human AML, treatment with ddC decreased mtDNA, electron transport chain proteins, and induced tumor ... ddC was preferentially activated in AML cells compared to normal hematopoietic progenitor cells. ddC treatment inhibited mtDNA ... in a subset of primary human leukemia cells and selectively targeted leukemia cells while sparing normal progenitors cells. ...

*  Preservation of Genomic Integrity in Mouse Embryonic Stem Cells | SpringerLink

Analysis of genetic instability during mammary tumor progression using a novel selection-based assay for in vivo mutations in a ... Stress defense in murine embryonic stem cells is superior to that of various differentiated murine cells. Stem Cells 2004; 22: ... Human embryonic stem cells have enhanced repair of multiple forms of DNA damage. Stem Cells 2008; 26:2266-2274.CrossRefPubMed ... Preservation of Genomic Integrity in Mouse Embryonic Stem Cells. In: Meshorer E., Plath K. (eds) The Cell Biology of Stem Cells ...

*  Assay of Tumorigenicity in Nude Mice

... invasion and wound healing of cell and tissue culture associated techniques ... assay of tumorigenicity in nude mice in assays of cell transformation, tumorigenesis, ... Hamburger, A. W., and Salmon, S. E. (1977). Primary bioassay of human tumor stem cells. Science 197, 461-463. Iiaza, T., Momiki ... potential of a cell line can be assayed by implanting tumor cells at the edge of rabbit cornea or by incubating it with tumor ...

*  Heidrun Karlic

tumor stem cell assay*carnitine o palmitoyltransferase*organic cation transport proteins*vegetarian diet*tumor stem cells* ... Tumor stem cell research - basis and challenge for diagnosis and therapy]. Heidrun Karlic. Ludwig Boltzmann Cluster Oncology ... Tumor stem cell research - basis and challenge for diagnosis and therapy]. Heidrun Karlic. Ludwig Boltzmann Cluster Oncology ... Our data indicate that OCNs mRNA and OCN protein is expressed in c-KIT positive neoplastic stem cells in hematological ...

*  R Baffa

tumor stem cell assay*butylhydroxybutylnitrosamine*micrornas*molecular biology*gene therapy*neoplasm rna*colonic neoplasms* ... tumor suppressor genes*neoplastic cell transformation*biological tumor markers*molecular cloning*down regulation*cell movement* ... Cell 85:17-26. 1996. ..Small cell lung cancer tumors and cell lines were analyzed by Southern blotting and showed rearranged ... Potential gastrointestinal tumor suppressor locus at the 3p14.2 FRA3B site identified by homozygous deletions in tumor cell ...

*  Human Oncogenes & Tumor Suppressor Genes EpiTect Chip qPCR Array

Assay. The purified ChIP DNA samples were characterized using Mouse Stem Cell Transcription Factor ChIP PCR Array with 1/100th ... Stem Cell Research. Stem cell differentiation into specific tissues involves the complex yet coordinated action of many ... The ChIP PCR Arrays can be used for research on stem cells, cancer, immunology, stem cells, toxicology, biomarker discovery and ... Cells from MCF-7 (1 million per sample) were subjected to ChIP assay with anti-RNA Polymerase II (Pol 2) antibody followed by ...

Stem cell theory of aging: The stem cell theory of aging is a new theory which was formulated by several scientists and which postulates that the aging process is the result of the inability of various types of stem cells to continue to replenish the tissues of an organism with functional differentiated cells capable of maintaining that tissue's (or organ's) original function. Damage and error accumulation in genetic material is always a problem for systems regardless of the age.Renal stem cell: Renal stem cells are self-renewing, multipotent stem cells which are able to give rise to all the cell types of the kidney. It is involved in the homeostasis and repair of the kidney, and holds therapeutic potential for treatment of kidney failure.Myeloid: The term myeloid (myelogenous) is an adjective that can refer to a progenitor cell for granulocytes, monocytes, erythrocytes, or platelets. Myeloid can be distinguished from the lymphoid progenitor cells that give rise to B cells and T cells.Neurooncology: Neuro-oncology is the study of brain and spinal cord neoplasms, many of which are (at least eventually) very dangerous and life-threatening (astrocytoma, glioma, glioblastoma multiforme, ependymoma, pontine glioma, and brain stem tumors are among the many examples of these). Among the malignant brain cancers, gliomas of the brainstem and pons, glioblastoma multiforme, and high-grade (highly anaplastic) astrocytoma are among the worst.Giant-cell glioblastoma: The giant-cell glioblastoma is a histological variant of glioblastoma, presenting a prevalence of bizarre, multinucleated (more than 20 nuclei) giant (up to 400 μm diameter) cells.Human embryonic stem cells clinical trials: ==Human Embryonic Stem Cell Clinical Trials==Cancer biomarkers: A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer.Tumor-associated glycoprotein: Tumor-associated glycoproteins (TAGs) are glycoproteins found on the surface of many cancer cells. They are mucin-like molecules with a molar mass of over 1000 kDa.SEA Native Peptide LigationCD36 antigen: CD36 antigen is a transmembrane, highly glycosylated, glycoprotein expressed by monocytes, macrophages, platelets, microvascular endothelial cells and adipose tissues. CD36 recognises oxidized low density lipoprotein, long chain fatty acids, anionic phospholipids, collagen types I, IV and V, thrombospondin and Plasmodium falciparum infected erythrocytes.Flow cytometry: In biotechnology, flow cytometry is a laser-based, biophysical technology employed in cell counting, cell sorting, biomarker detection and protein engineering, by suspending cells in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and chemical characteristics of up to thousands of particles per second.Pluripotency (biological compounds): The pluripotency of biological compounds describes the ability of certain substances to produce several distinct biological responses. Pluripotent is also described as something that has no fixed developmental potential, as in being able to differentiate into different cell types in the case of pluripotent stem cells.Hematopoietic stem cell transplantationNude mouseAntileukemic drug: Antileukemic drugs, anticancer drugs that are used to treat one or more types of leukemia, include:Gliogenesis: Gliogenesis is the generation of non-neuronal glia populations derived from multipotent neural stem cells.Stemgent: Stemgent is an American privately funded biotech company focused on providing reagents and technology developed by some of the world's leading stem cell scientists. Founded in 2008, Stemgent has two fully operational facilities in both San Diego, California and Cambridge, Massachusetts.Matrix model: == Mathematics and physics ==SB-431542Ancestim

(1/1173) Combination interferon-alpha2a and 13-cis-retinoic acid enhances radiosensitization of human malignant glioma cells in vitro.

We investigated the individual and combined effects of cis-retinoic acid (CRA) and/or IFN-alpha (IFN) and/or radiation therapy (RT) against a human glioma cell line (American Type Culture Collection; U373MG) to evaluate the possible radiosensitization properties of these agents in vitro. Glioma cells were incubated for 24 h in 96-well plates (2 x 10(2) cells/well) in standard culture medium. Sets of U373 (n = 12) were exposed to CRA (3 x 10(6) microM), IFN (25 units/ml), CRA plus IFN, or standard culture medium. After an additional 24 h of incubation, the U373 cells were subjected to increasing radiation doses (up to 16 Gy). Glioma cells were harvested 92 h after irradiation, and cell survival curves were determined from [3H]thymidine incorporation data (over the last 24 h). The experiment was repeated for both the untreated control group and the combined CRA/IFN group. To verify the [3H]thymidine assays, a clonogenic assay was also performed. Single cell suspensions of U373 cells were plated out in six-well plates (n = 3). After chemical and RT treatment, colonies of 50 cells or more were counted, and cell survival curves were generated as fractions of nonirradiated controls. The amount of RT (in Gy) that would cause a 50% survival fraction (lethal dose 50 or LD50) was calculated from the survival curves by regression analysis. The following LD50s were obtained: [table: see text] The results showed that for both the [3H]thymidine incorporation assay and the clonogenic assay, the combination of IFN/CRA rendered U373 cells more susceptible to ionizing radiation than the untreated control or either single agent alone.  (+info)

(2/1173) Inhibition of aberrant proliferation and induction of apoptosis in HER-2/neu oncogene transformed human mammary epithelial cells by N-(4-hydroxyphenyl)retinamide.

Epithelial cells from non-cancerous mammary tissue in response to exposure to chemical carcinogens or transfection with oncogenes exhibit hyperproliferation and hyperplasia prior to the development of cancer. Aberrant proliferation may, therefore, represent a modifiable early occurring preneoplastic event that is susceptible to chemoprevention of carcinogenesis. The synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR), has exhibited preventive efficacy in several in vitro and in vivo breast cancer models, and represents a promising chemopreventive compound for clinical trials. Clinically relevant biochemical and cellular mechanisms responsible for the chemopreventive effects of HPR, however, are not fully understood. Experiments were performed on preneoplastic human mammary epithelial 184-B5/HER cells derived from reduction mammoplasty and initiated for tumorigenic transformation by overexpression of HER-2/neu oncogene, to examine whether HPR inhibits aberrant proliferation of these cells and to identify the possible mechanism(s) responsible for the inhibitory effects of HPR. Continuous 7-day treatment with HPR produced a dose-dependent, reversible growth inhibition. Long-term (21 day) treatment of 184-B5/HER cells with HPR inhibited anchorage-dependent colony formation by approximately 80% (P < 0.01) relative to that observed in the solvent control. A 24 h treatment with cytostatic 400 nM HPR produced a 25% increase (P = 0.01) in G0/G1 phase, and a 36% decrease (P = 0.01) in S phase of the cell cycle. HPR treatment also induced a 10-fold increase (P = 0.02) in the sub-G0 (apoptotic) peak that was down-regulated in the presence of the antioxidant N-acetyl-L-cysteine. Treatment with HPR resulted in a 30% reduction of cellular immunoreactivity to tyrosine kinase, whereas immunoreactivity to p185HER remained essentially unaltered. HPR exposure resulted in time-dependent increase in cellular metabolism of the retinoid as evidenced by increased formation of the inert metabolite N-(4-methoxyphenyl)-retinamide (MPR) and progressive increase in apoptosis. Thus, HPR-induced inhibition of aberrant proliferation may be caused, in part, by its ability to inhibit HER-2/neu-mediated proliferative signal transduction, retard cell cycle progression and upregulate cellular apoptosis.  (+info)

(3/1173) RSR13, an allosteric effector of haemoglobin, and carbogen radiosensitize FSAII and SCCVII tumours in C3H mice.

Pre-clinical evaluation has demonstrated that 2-[4-(((3,5-dimethylanilino)carbonyl)methyl)phenoxy]-2-methylpropi onic acid (RSR13) acts as an allosteric effector of haemoglobin (Hb). RSR13 binding to Hb results in decreased haemoglobin-oxygen (Hb-O2) affinity, improved tumour oxygenation, and enhanced radiation-induced cell killing in several experimental tumour systems. In the present work, ex vivo clonogenic survival analyses are applied in two murine tumour systems to characterize the relationship between the magnitude of decrease in Hb-O2 affinity and radiosensitization, the influence of inspired pO2 upon this effect, and the efficacy of combining RSR13 and radiation during a course of repeated radiation exposures. For FSaII tumours in C3H mice breathing air, 100 mg kg(-1) RSR13 administered intraperitoneally produced an enhancement ratio (ER) of 1.3, but there was marked desensitization at a RSR13 dose of 300 mg kg(-1) (ER 0.6). The most likely reason for the increased radioresistance was insufficient oxygen loading of Hb in the pulmonary circulation due to reduced haemoglobin-oxygen affinity because carbogen breathing combined with 300 mg kg(-1) RSR13 reversed the effect and produced an ER of 1.8. In SCCVII tumours in C3H mice irradiated with eight fractions of 2.5 Gy over 4 days, the surviving fraction was reduced to 58-67% of control values when RSR13 was combined with radiation on days 1 and 2, days 3 and 4, or days 1-4. These results confirm that combining RSR13 and irradiation within a fractionated course of clinically relevant low-dose exposures provides significant radiosensitization. Additional preclinical experimentation is needed to define better the optimum dose-scheduling conditions for clinical applications.  (+info)

(4/1173) Cyclin D1 overexpression enhances radiation-induced apoptosis and radiosensitivity in a breast tumor cell line.

Overexpression of cyclin D1, a G1 cell cycle regulator, is often found in many different tumor types, such as breast carcinoma and squamous cell carcinoma of the head and neck. The overexpression of this protein is, in several cases, associated with a poor prognosis. In this study, the effect of cyclin D1 on radiosensitivity was investigated in a breast tumor cell line, MCF7, containing a cyclin D1 gene construct under the control of a tetracycline-sensitive regulator. MCF7 cells cultured without tetracycline resulted in a 6-fold increase in the cyclin D1 protein. Cyclin D1-overexpressing MCF7 cells were more sensitive to ionizing radiation than the nonoverexpressing counterparts. The cyclin D1-overexpressing cells also exhibited a higher induction of apoptosis. Treatment with a dose of 5 Gy resulted in a rapid increase of p53 and p21 in the cyclin D1-overexpressing cells. Nonoverexpressing cells showed a more transient expression of these proteins after ionizing radiation. A pronounced G2-M block was observed in both cell lines. The cyclin D1-overexpressing cells were, however, released earlier from the block than the control cells. These data suggest that overexpression of cyclin D1 alters sensitivity toward ionizing radiation by modulating gamma-radiation-induced G2-M transition.  (+info)

(5/1173) Malignant transformation of p53-deficient astrocytes is modulated by environmental cues in vitro.

The early incidence of p53 mutation in astrocytomas suggests that it plays an important role in astrocyte transformation. Astrocytes isolated from homozygous p53 knockout mice grow rapidly, lack contact inhibition, and are immortal. Here we tested whether the loss of p53 is sufficient for progression to tumorigenicity of astrocytes. We grew primary astrocytes under three conditions for over 120 population doublings and assessed their antigenic phenotype, chromosome number, and expression of glioma-associated genes as well as their ability to form colonies in soft agarose and tumors s.c. and intracranially in nude mice. Under two conditions (10% FCS and 0.5% FCS plus 20 ng/ml EGF), cells acquired the ability to form colonies in soft agarose and tumors in nude mice, and this was accompanied by the expression of genes, including epidermal growth factor receptor, platelet-derived growth factor receptor alpha and beta, protein kinase Cdelta, and vascular endothelial growth factor, which are known to be aberrantly regulated in human astrocytomas. Under the third condition (0.5% FCS plus 10 ng/ml basic fibroblast growth factor), astrocytes gained the ability to form colonies in soft agarose and had abnormal chromosome numbers similar to cells in the first two conditions but did not form tumors in nude mice or overexpress glioma-associated genes. These data provide experimental evidence for the idea that the malignant progression initiated by the loss of p53 may be subject to modulation by extracellular environmental influences.  (+info)

(6/1173) In vitro radiosensitivity of tumour cells and fibroblasts derived from head and neck carcinomas: mutual relationship and correlation with clinical data.

The aim was to characterize the variation in the cellular in vitro radiosensitivities in squamous cell carcinomas of the head and neck, and to test for a possible correlation between different measures of radiosensitivity and the clinical and histopathological data. Cellular in vitro radiosensitivities were assessed in tumour biopsies from 71 patients using the modified Courtenay-Mills soft agar clonogenic assay combined with an immunocytochemical analysis. Radiosensitivity was quantified as the surviving fraction after a radiation dose of 2 Gy irrespective of cell type (overall SF2), or based on identification of cell type (tumour cell SF2, fibroblast SF2). Sixty-three biopsies were from primary tumours, and eight were from recurrences. Overall plating efficiency ranged from 0.005 to 1.60% with a median of 0.052%. The majority of the colonies obtained from the biopsies were fibroblast marker-positive; the proportion of tumour marker-positive colonies ranged from 1 to 88% with a median of 15%. The median overall SF2 was 0.47 (range 0.24-0.96), the median tumour cell SF2 was 0.50 (range 0.11-1.0) and the median fibroblast SF2 was 0.49 (range 0.24-1.0). Comparing data from independent experiments, the overall SF2 was significantly correlated with the SF2 of fibroblasts (2P = 0.006) but not with the tumour cell SF2. The tumour cell and fibroblast radiosensitivities measured in the same individuals were not correlated (r= 0.06, 95% CI [-0.19, 0.30]):This finding seems to preclude a strong correlation between the radiosensitivity of tumour cells and fibroblasts. Concerning the clinical characteristics, neither of the measures of tumour radiosensitivity was correlated with T- and N-category, stage, tumour size, sex and age. However, the tumour cell radiosensitivity decreased with increasing grade of histopathological differentiation (2P = 0.012). The same tendency was found in two independent analyses of the same patient material. This correlation was not significant in case of the overall SF2 or the fibroblast SF2.  (+info)

(7/1173) Up-regulation of E-cadherin by an anti-epidermal growth factor receptor monoclonal antibody in lung cancer cell lines.

Many human epithelial carcinomas are characterized by the overexpression and constitutive activation of the epidermal growth factor receptor (EGF-R) via an autocrine signaling loop. We have investigated the effects of a ligand-blocking monoclonal antibody (mAb) against the EGF-R LA1 on selected parameters of human lung cancer cell lines (H322 and H661) and normal human bronchial epithelial (NHBE) cells. Using Western blot analysis, we show that H322 and NHBE cell lines express comparable levels of EGF-R/p170erbB-1. The LA1 mAb against EGF-R inhibits growth, induces differentiation to a more epithelial phenotype, reduces the constitutive activation of EGF-R, and upregulates epithelial cadherin glycoprotein expression in H322 and NHBE cells. In contrast, LA1 had no effect on either growth, differentiation, receptor tyrosine phosphorylation, or the expression of adhesion molecules in H661 cells, which is consistent with our finding that this cell line does not express detectable levels of EGF-R. These studies demonstrate that a blocking anti-EGF-R mAb can regulate proliferation, differentiation, and the expression of cell adhesion molecules in human bronchial epithelial cells. Our findings suggest possible therapeutic avenues for the treatment of invasive carcinomas via the blockade of EGF-R with antibodies.  (+info)

(8/1173) Influence of O6-benzylguanine on the anti-tumour activity and normal tissue toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea and molecular combinations of 5-fluorouracil and 2-chloroethyl-1-nitrosourea in mice.

Previous studies have demonstrated that novel molecular combinations of 5-fluorouracil (5FU) and 2-chloroethyl-1-nitrosourea (CNU) have good preclinical activity and may exert less myelotoxicity than the clinically used nitrosoureas such as 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). This study examined the effect of O6-alkylguanine-DNA-alkyltransferase (ATase) depletion by the pseudosubstrate O6-benzylguanine (BG) on the anti-tumour activity and normal tissue toxicity in mice of three such molecular combinations, in comparison with BCNU. When used as single agents at their maximum tolerated dose, all three novel compounds produced a significant growth retardation of BCNU-resistant murine colon and human breast xenografts. This in vivo anti-tumour effect was potentiated by BG, but was accompanied by severe myelotoxicity as judged by spleen colony forming assays. However, while tumour resistance to BCNU was overcome using BG, this was at the expense of enhanced bone marrow, gut and liver toxicity. Therefore, although this ATase-depletion approach resulted in improved anti-tumour activity for all three 5-FU:CNU molecular combinations, the potentiated toxicities in already dose-limiting tissues indicate that these types of agents offer no therapeutic advantage over BCNU when they are used together with BG.  (+info)



subpopulation

  • Telomerase was undetectable in the majority of tumor cells and specific to the TIC subpopulation that possessed critically short telomeres. (aacrjournals.org)
  • This study reveals that telomerase activation exists only in the tumor-initiating cancer subpopulation and is critical to sustain their survival and self-renewal potential. (aacrjournals.org)
  • Cancer stem/progenitor cells (CSCs) are a subpopulation of cancer cells involved in tumor initiation, resistance to therapy and metastasis. (mdpi.com)
  • Identification of an ABCB1 (P-glycoprotein)-positive carfilzomib-resistant myeloma subpopulation by the pluripotent stem cell fluorescent dye CDy1. (althotas.com)
  • The cancer stem cell hypothesis postulates that a small subpopulation of chemotherapy-resistant cancer cells is responsible for propagation of the tumor. (althotas.com)
  • Herein we report that efflux of the pluripotent stem cell dye CDy1 identifies a subpopulation in MM cell lines characterized by increased expression of P-glycoprotein, a member of the ABC (ATP-binding cassette) superfamily of transporters encoded by ABCB1. (althotas.com)

Inhibition

  • Because telomerase is thought to be active in all tumor cells and normal stem cells, telomerase inhibition may be nonspecific and have detrimental effects on tissue maintenance and development by affecting normal stem cell self-renewal. (aacrjournals.org)
  • In contrast, normal tissue stem cells had longer telomeres and undetectable telomerase activity and were insensitive to telomerase inhibition, which results in proliferation arrest, cell maturation, and DNA damage in neural TIC. (aacrjournals.org)
  • TIC exhaustion with telomerase inhibition and lack of telomerase dependency in normal stem cells add new dimensions to the telomere hypothesis and suggest that targeting TIC with telomerase inhibitors may represent a specific and safe therapeutic approach for tumors of neural origin. (aacrjournals.org)
  • Furthermore, as opposed to conventional chemoradiation therapies, telomerase inhibition results in irreversible loss of self-renewal capacity of tumor initiating cells in vitro and in vivo . (aacrjournals.org)
  • These observations uncover a difference between normal and cancer stem cell biology in the nervous system and suggest that telomerase inhibition may offer a specific and safe therapeutic approach for these devastating tumors. (aacrjournals.org)

malignant

  • Telomerase is active in most malignant pediatric neural tumors. (aacrjournals.org)
  • Multiple myeloma (MM) is characterized by the malignant expansion of differentiated plasma cells. (althotas.com)

self-renewal

  • Prostate cancer stem cells (PCSCs) have been identified as a low frequency cell population capable of self-renewal and differentiation, which are believed to play an essential role in cancer recurrence following therapeutic intervention [ 3 - 5 ]. (mdpi.com)
  • We then tested the efficacy of the telomerase inhibitor Imetelstat on propagation and self-renewal capacity of TIC and normal stem cells in vitro and in vivo . (aacrjournals.org)
  • Furthermore, neural TIC exhibited irreversible loss of self-renewal and stem cell capabilities even after cessation of treatment in vitro and in vivo . (aacrjournals.org)
  • Because normal stem cells may require telomerase for continuous self-renewal, this therapy may have devastating effects on normal nervous system development and maintenance. (aacrjournals.org)
  • Importantly, normal neural or neural crest stem cells do not require telomerase for their self-renewal. (aacrjournals.org)
  • Limitless self-renewal is necessary for these tumors for continuous recurrence. (aacrjournals.org)
  • Ova also inhibited the self-renewal capability of breast CSCs (BCSCs) which was determined by mammosphere assay. (mdpi.com)

therapeutic

  • Overexpression of Hsp27 or knockdown of SMURF2 in AS-B145 cells diminished the therapeutic effect of ovatodiolide in the suppression of mammosphere formation. (mdpi.com)

vitro

  • We further show that chemosensitization of MM cells to carfilzomib could be achieved in vitro by cotreatment with vismodegib, a hedgehog pathway antagonist which is currently in MM clinical trials. (althotas.com)

propagation

  • Although prostate cancer stem cells have been successfully identified, the molecular pathways regulating their generation and propagation are poorly understood. (mdpi.com)

Therefore

  • CDy1 efflux may therefore be a useful assay to determine whether high expression of ABCB1 is predictive of poor clinical responses in MM patients treated with carfilzomib. (althotas.com)

proliferation

  • Enhancer of zeste homolog 2 (EZH2) plays a crucial role in embryonic and somatic stem cells for their proliferation and differentiation. (mdpi.com)
  • We first discovered that Ova displayed an anti-proliferation activity in these two breast cancer cells. (mdpi.com)

resistance

  • Moreover, increased resistance to carfilzomib in sensitive MM cells following drug selection was associated with upregulation of ABCB1 cell-surface expression which correlated with increased transporter activity as measured by CDy1 efflux. (althotas.com)

Therapy

  • These tumors, specifically gliomas and neuroblastomas, share unique extremes of clinicobiological behavior: spontaneous growth arrest, on the one hand, and relentless progression even with maximal therapy, on the other ( 2 , 3 ). (aacrjournals.org)
  • We also demonstrate that ABCB1-overexpressing MM cells are resistant to the second-generation proteasome inhibitor carfilzomib that recently received accelerated approval for the treatment of therapy-refractive MM by the U.S. Food and Drug Administration. (althotas.com)

molecular

  • This can be explained by telomere maintenance on the molecular level and existence of tumor-initiating cells (TIC) on the cellular level. (aacrjournals.org)

Cytotoxic

  • Although many chemotherapeutic agents display cytotoxic activity toward MM cells, patients inevitably succumb to their disease because the tumor cells become resistant to the anticancer drugs. (althotas.com)

methods

  • PCSCs have been isolated from prostate carcinoma and prostate cancer cell lines using several methods, including flow cytometry for specific cell surface markers, isolation of a side population, and formation of cell spheres [ 6 - 9 ]. (mdpi.com)

lines

  • We examined telomerase activity, telomere maintenance, and stem cell maturation in tumor subpopulations from freshly resected gliomas, long-term, primary, neural tumor-initiating cells (TIC) and corresponding normal stem cell lines. (aacrjournals.org)
  • Here we used two human breast cancer cell lines (AS-B145 and BT-474) to examine the effect of Ova on breast CSCs. (mdpi.com)

responsible

  • Pediatric central and peripheral nervous system tumors comprise the largest group of childhood solid tumors and are responsible for the most morbidity and mortality from childhood cancer ( 1 ). (aacrjournals.org)

expression

  • Furthermore, EZH2 was a direct target of miR-101 in PCSCs and EZH2's mRNA levels were inversely correlated with miR-101 expression and cyclin E2 (a cell-cycle regulator) was suppressed by siEZH2. (mdpi.com)
  • Ova dose-dependently downregulated the expression of stemness genes, octamer-binding transcription factor 4 (Oct4) and Nanog, as well as heat shock protein 27 (Hsp27), but upregulated SMAD ubiquitin regulatory factor 2 (SMURF2) in mammosphere cells derived from AS-B145 or BT-474. (mdpi.com)

growth

  • Cell growth was investigated by MTT, cell cycle and apoptosis of PCSCs were explored by flow cytometric analysis. (mdpi.com)
  • Silence of EZH2 inhibited cell growth and the cell cycle and promoted the progression of apoptosis. (mdpi.com)
  • Significant survival benefit and late tumor growth arrest of neuroblastoma TIC were observed in a xenograft model ( P = 0.02). (aacrjournals.org)

level

  • Finally, the upstream pathway miRNA level was determined via a luciferase reporter assay, and the downstream pathway cycle regulators were examined via reverse transcriptase-polymerase chain reaction. (mdpi.com)

results

  • The results showed that LNcap cell line comprised a greater proportion of CD44 + /CD133 + cells by comparison to the PC-3 cell line. (mdpi.com)

human

  • PCSCs were isolated from the human prostate cancer cell line LNcap by fluorescence activated cell sorting (FACS). (mdpi.com)