It has recently been shown that central nervous system stem cells and haematopoietic stem cells and early progenitors contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. Data from individual tumor phenotypic analysis and serial transplants performed in limiting dilution show that residual tumors are enriched for cells with the CoCSC phenotype and have increased tumorigenic cell frequency. The wild-type p53/GFP fusion protein was localized in the cytoplasm, the nucleus, or both compartments in a subset of the cells. The theory of cancer stem cells states that a subset of cancer cells within a tumor has the ability to self-renew and differentiate. Clarke, M. F., Fitzgerald, P. C., Brubaker, J. M., Simpson, R. T. DNA METHYLATION AND EXPRESSION OF HLA-DR-ALPHA. However, the bone marrow of such patients is often contaminated with tumor cells. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. These results indicate that the CSD can regulate p53 nuclear import by controlling access of the NLS to importin alpha binding. Professor, Philosophy; Associate Professor, Classics npappas@gc.cuny.edu John D. Greenwood Deputy Executive Officer and Professor, Philosophy; Professor, Psychology +1 212-817-8617 jgreenwood@gc.cuny.edu Natile Clarke Assistant Program Officer, Philosophy +1 212-817-8623 nclarke@gc.cuny.edu Limiting dilution transplantations of breast epithelial cells devoid of TLR2 or MYD88 revealed a significant decrease in mammary repopulating unit frequency compared with the control. However, at later times X-ray irradiated parental DP16-1 cells also had decreased survival compared to the unirradiated control. Thus, loss of expression of the alpha-catenin tumor suppressor in hematopoietic stem cells may provide a growth advantage that contributes to human MDS or AML with del(5q). Usp16 regulation of the Wnt pathway in mouse and human tissues is at least in part mediated by activation of Cdkn2a, a regulator of senescence. View details for DOI 10.1016/j.stem.2009.05.019, View details for Web of Science ID 000269511900010. View details for Web of Science ID A1995RC93600007. Here we show that bone marrow cells from mice deficient in three genes genetically downstream of Bmi1--p16Ink4a, p19Arf and Trp53 (triple mutant mice; p16Ink4a and p19Arf are alternative reading frames of the same gene (also called Cdkn2a) that encode different proteins)--have an approximately 10-fold increase in cells able to reconstitute the blood long term. View details for DOI 10.1016/j.semradonc.2008.11.002, View details for Web of Science ID 000264310800003, View details for PubMedCentralID PMC2789266. James H. Clarke, Michael P. Vandenbergh . Email: charlotte.clarke@ed.ac.uk. The N-bGM-CSFs demonstrated GM-CSF receptor specific binding that was displaceable by excess underivatized protein, with the detected fluorescence signal decreasing with increasing biotin to protein molar ratio. When viability was measured 24 h post-radiation, cells that had been briefly exposed to wtp53 immediately after X-ray irradiation had decreased survival as compared to unirradiated cells expressing wtp53 or X-ray irradiated DP16-1 cells. We developed a new technique that replaces immunoprecipitation with a simplified chromatin fragmentation and proximity ligation step that eliminates bead purification and washing steps. Many of these mutations affect cell proliferation and survival. The results of in vitro GTPase single-turnover assays using Galpha(i) indicated that RGS18 accelerates the intrinsic GTPase activity of Galpha(i). He is member of the Board of Parks Victoria. View details for Web of Science ID A1984TC73000037. In the accompanying paper it was shown that all T cells producing HTLV, whether cultured from infected persons or infected in vitro, bind a monoclonal antibody (4D12) which recognizes an epitope shared by certain cross-reactive class I major histocompatibility antigens. Understanding and reproducing the molecular interactions between bone marrow stromal cells and stem cells in tissue culture models is therefore the critical step in successful bone marrow tissue culture. Sumantran, V. N., Ealovega, M. W., Nunez, G., Clarke, M. F., Wicha, M. S. In vitro expansion of hematopoietic cells for clinical application. The data clearly indicate, however, that the class I and class II components of the major histocompatibility complex are unusually hypermethylated in several T-ALL-derived cell lines, while ATL T-cell lines do not substantially differ in this respect from normal peripheral blood T-cells. Tumor kinetic rate constants (K1, k2, k3) and net rate of FDG phosphorylation (K = [K1.k3]/[k2 + k3]) in tumors were calculated from the dynamic data by means of a three-compartment model, assuming k4 = 0.Viable tumors (n = 10) showed intense FDG uptake and could easily be differentiated visually from mature teratoma (n = 6) and necrosis or scar (n = 10). Herrema I, Clarke M. Anaesthesia for retinoblastoma screening - a dilemma. INGRAHAM, L. M., Weening, R. S., Clarke, M. F., Boxer, L. A., Baehner, R. L. Freeman Spogli Institute for International Studies, Institute for Computational and Mathematical Engineering (ICME), Institute for Human-Centered Artificial Intelligence (HAI), Institute for Stem Cell Biology and Regenerative Medicine, Stanford Institute for Economic Policy Research (SIEPR), Stanford Woods Institute for the Environment, Office of VP for University Human Resources, Office of Vice President for Business Affairs and Chief Financial Officer, Directed Reading in Stem Cell Biology and Regenerative Medicine, Stem Cell Biology and Regenerative Medicine (Phd Program), DOI 10.1146/annurev.cellbio.22.010305.104154. We report here that the genes for HLA class I antigens are also highly methylated in the T-ALL T-cell lines relative to the same genes in the ATL T-cell lines, normal peripheral blood T cells, and autologous normal B-cell lines. Conversely, genetic augmentation of Hedgehog response and systemic small-molecule Hedgehog pathway activation potently ameliorate colitis and restrain initiation and progression of colitis-induced adenocarcinoma. Tumors injected four times with the bcl-xs adenovirus showed a 50% reduction in size. Recently, various new players that regulate HSC maintenance (e.g. Stem cells in normal breast development and breast cancer. We performed multiplexed single-cell gene expression analysis with quantitative reverse transcriptase polymerase chain reaction followed by hierarchical clustering analysis to characterize distinct cell types. These latter cell lines do express HLA-DR alpha-mRNA, as well as HLA-DR surface antigens. We will discuss the important implications of this mammary tumour stem-cell model. CD137 activation, which was dependent on NK cell expression of the FcRIII receptor, occurred both in vitro and in the peripheral blood of women with HER2-expressing breast cancer after trastuzumab treatment. Isobe, T., Zarneger, M. A., Matsubara, J., Abdel-Wahab, O., Clarke, M. F. Usp16 modulates Wnt signaling in primary tissues through Cdkn2a regulation. These chemically reactive forms of biotin produced derivatives biotinylated at amine or carboxyl groups, respectively. Direct visualization of human tumor cells in vivo shows two patterns of high-speed migration inside primary tumors: (1) single cells and (2) multicellular streams (i.e., cells following each other in a single file but without cohesive cell junctions). Dr. Michael F. Clarke is the Karel and Avice Beekhuis Professor in Cancer Biology and Associate Director of the Stanford Institute for Stem Cell and Regenerative Medicine. We developed an immunodeficient mouse model to test the tumorigenic potential of different populations of cancer cells derived from primary, unmanipulated human HNSCC samples. A., Spallino, E., Aaron, K. A., Concepcion, W., Gardner, J. M., Kelly, B., Neidlinger, N., Wang, Z., Crasta, S., Kolluru, S., Morri, M., Tan, S. Y., Travaglini, K. J., Xu, C., Alcantara-Hernandez, M., Almanzar, N., Antony, J., Beyersdorf, B., Burhan, D., Calcuttawala, K., Carter, M. M., Chan, C. K., Chang, C. A., Chang, S., Colville, A., Culver, R. N., Cvijovic, I., D'Amato, G., Ezran, C., Galdos, F. X., Gillich, A., Goodyer, W. R., Hang, Y., Hayashi, A., Houshdaran, S., Huang, X., Irwin, J. C., Jang, S., Juanico, J. V., Kershner, A. M., Kim, S., Kiss, B., Kong, W., Kumar, M. E., Kuo, A. H., Leylek, R., Li, B., Loeb, G. B., Lu, W., Mantri, S., Markovic, M., McAlpine, P. L., de Morree, A., Mrouj, K., Mukherjee, S., Muser, T., Neuhofer, P., Nguyen, T. D., Perez, K., Phansalkar, R., Puluca, N., Qi, Z., Rao, P., Raquer-McKay, H., Schaum, N., Scott, B., Seddighzadeh, B., Segal, J., Sen, S., Sikandar, S., Spencer, S. P., Steffes, L., Subramaniam, V. R., Swarup, A., Swift, M., Van Treuren, W., Trimm, E., Veizades, S., Vijayakumar, S., Vo, K. C., Vorperian, S. K., Wang, W., Weinstein, H. N., Winkler, J., Wu, T. T., Xie, J., Yung, A. R., Zhang, Y., Detweiler, A. M., Mekonen, H., Neff, N. F., Sit, R. V., Tan, M., Yan, J., Bean, G. R., Charu, V., Forgo, E., Martin, B. Many cancers overexpress a member of the bcl-2 family of inhibitors of apoptosis. Loss of Bcl11b leads to a Cdkn2a-dependent exhaustion of ductal epithelium and loss of epithelial cell regenerative capacity. Fundamentally, the system is the paradigm of a complex interactive tissue, in which the proliferation and regulated differentiation of one parenchymal cell type (the hematopoietic stem cell) is governed by the surrounding stromal cells. School of Civil Engineering +61 7 336 56464. william.clarke@uq.edu.au. Disruption of the regulation of self-renewal results in cancer. In this study we describe the effect on murine erythroleukemia cells, transfected with a temperature-sensitive mutant p53, of exposure to the differentiating agent dimethylsulfoxide (DMSO). Yoo, S., Chandhasin, C., Del Rosario, J. R., Chen, Y. K., Stafford, J., Quake, S., Perabo, F., Clarke, M. F. Pharmacologic characterization of TACH101, a first-in-class KDM4 inhibitor for development as a cancer therapeutic. Clarke, M. F., Gelmann, E. P., Reitz, M. S. RELATION OF RESPIRATORY BURST AND ARACHIDONATE METABOLISM DURING PHAGOCYTOSIS BY GUINEA-PIG ALVEOLAR MACROPHAGES. Analysis of the surface molecule repertoire of EpCAM(high)/CD44+ cells led to the identification of CD166 as an additional differentially expressed marker, useful for CSC isolation in three of three CRC tested. Arthur Thomas Malkin (1803-1888), Pionier der Bergsteigerei und Schriftsteller. Genomic DNA extracted at 32.5 degrees C was seen to be fragmented into a characteristic ladder consistent with cell death due to apoptosis. View details for Web of Science ID 000089592300005. Clarke, M. F., KukowskaLatallo, J. F., Westin, E., Smith, M., Prochownik, E. V. ACTIVATION OF A NOVEL KPNI TRANSCRIPT BY DOWNSTREAM INTEGRATION OF A HUMAN T-LYMPHOTROPIC VIRUS TYPE-I PROVIRUS. Free UK delivery for orders 30 and over. Using these targeted reporter mice, we demonstrated that Bmi-1 is expressed in hematopoietic stem cells (HSCs) at its highest levels and downregulated upon commitment to differentiation. The lactate/glucose and ammonia/glutamine yield coefficients, however, remained invariant at about 1.9 and 1.0 mol/mol, respectively, under all medium perfusion conditions. Murine RV EW robustly activated type I IFNs and several antiviral genes (IFN-stimulated genes) in the intestine by bulk analysis, the source of induced IFNs primarily being hematopoietic cells. Finally, we show evidence that these properties are maintained in the context of an adenoviral vector (AdEHhrk). These studies suggest that adenovirus suicide vectors may provide a simple and effective method to selectively eliminate cancer cells derived from epithelial tissue that contaminate bone marrow to be used for autologous BMT. SMAD pathways govern epithelial proliferation, and transforming growth factor beta (TGF-beta and BMP signaling through SMAD members has distinct effects on mammary development and homeostasis. Clarke M, Mitchell KW, Goodship J, McDonnell S, Barker MD, Griffiths ID, McKie N. Clinical features of a novel TIMP-3 mutation causing Sorsby's fundus dystrophy: implications for disease mechanism. Treatment of these T-cells with 5-azacytidine resulted in the induction of DR surface antigen expression, the appearance of DR alpha mRNA, and the partial demethylation of the DR alpha DNA sequences. 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