Liu, H., Shimono, Y., Bockhorn, J., Olopade, F., Greene, G., Clarke, M. F. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Ayash, L. J., Clarke, M., Silver, S. M., Braun, T., Uberti, J., Ratanatharathorn, V., Reynolds, C., Ferrara, J., Broun, E. R., Adams, P. T. Evaluation of a new dual-specificity promoter for selective induction of apoptosis in breast cancer cells. By creating monoclonal tumor xenografts from injection of a single (n = 1) cell, we demonstrate that the transcriptional diversity of cancer tissues is largely explained by in vivo multilineage differentiation and not only by clonal genetic heterogeneity. Taken together, these data demonstrate that cells within the CD44(+) population of human HNSCC possess the unique properties of cancer stem cells in functional assays for cancer stem cell self-renewal and differentiation and form unique histological microdomains that may aid in cancer diagnosis. Control experiments show that positioning is not due to the 21-bp repeats or to end effects. View details for DOI 10.1038/s41598-018-34562-w, View details for Web of Science ID 000451748700028. To investigate the possible role of Bmi-1 in other cell types that also self-renew, we generated Bmi-1-green fluorescent protein (GFP)-knock-in mice, in which GFP was expressed under the endogenous transcriptional regulatory elements of the Bmi-1 gene. Park, I., Qian, D., Kiel, M., Becker, M., Prohaska, S., Weissman, I., Morrison, S., Clarke, M. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. My research is located in three overlapping fields: (a) linguistic and cultural transfer from Mediterranean Antiquity to the medieval European vernaculars; (b) comparative study of epic and heroic narrative traditions, especially in Greek, Latin, and Babylonian, and of their Celtic and Germanic successors and analogues; (c) semantic View details for Web of Science ID 000345777300014. A., Chen, L., Levy, R. Removal of lactate dehydrogenase-elevating virus from human-in-mouse breast tumor xenografts by cell-sorting. Differential regulation of medium versus serum perfusion demonstrated that increased NIH-3T3 cell metabolism was directly proportional to the serum flux to which the cells were exposed. Adorno, M., Sikandar, S., Mitra, S. S., Kuo, A., Nicolis Di Robilant, B., Haro-Acosta, V., Ouadah, Y., Quarta, M., Rodriguez, J., Qian, D., Reddy, V. M., Cheshier, S., Garner, C. C., Clarke, M. F. Identification of a cKit(+) Colonic Crypt Base Secretory Cell That Supports Lgr5(+) Stem Cells in Mice. Stanford is currently not accepting patients for this trial. Orthologs of these differentially expressed genes predicted survival of human breast cancer patients from two different study groups. Dontu, G., Al-Hajj, M., Abdallah, W. A., Clarke, M. F., Wicha, M. S. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Most cancers comprise a heterogenous population of cells with marked differences in their proliferative potential as well as the ability to reconstitute the tumor upon transplantation. It was found that a single mutation of Arg-306 resulted in the defect of p53 nuclear import. Our study demonstrates that microRNA-30c is transcriptionally regulated by GATA3 in breast tumours. It is most highly expressed in bone marrow followed by fetal liver, spleen, and then lung. When breast cancer cells mixed with hematopoietic cells were infected with the bcl-x(s) adenovirus, cancer cells were selectively killed by the suicide adenoviruses. Both VIM and TWF1 have been shown to regulate epithelial-to-mesenchymal transition. 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. Cancer stem cells are a minor population of tumor cells that possess the stem cell property of self-renewal. Anaesthesia 2001, 56(5), 486-487. With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. Just months into the Biden-Harris administration, the change in tone, message, and approach to transatlantic relations is palpable. This will allow the characterization of crucial signaling pathways involved in processes such as self-renewal that are critical for tumor formation by the cancer cells within de novo tumors. In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein-negative colon cancers than among the 276 (87.9%) with CDX2 protein-positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P=0.003). In culture, codelivery of virus and pE1 resulted in a large increase in infected cells when compared with control cells exposed to virus and pUC19. Associate Professor of Instruction; PhD. B., Lu, R., Attema, J. L., Lobo, N. A., Weissman, I. L., Clarke, M. F., Quake, S. R. Optimized imaging of the growth and metastasis of human breast cancer stem cells in immunodeficient mice. 3-7), attempts to identify tumor suppressors within this band have been unsuccessful. Professor Clarke is a former Deputy Vice . The retrovirus transduced culture continued to produce genetically modified hematopoietic progenitors for up to 6 weeks, the duration of the culture period. The aim of the present study was to determine the effects of Bcl-xS expression on the viability of NB cells. As well as addressing the patient's medical needs, these highly trained professionals . The effect of these changes on protein function is currently unknown. Here, we identify a quiescent mammary epithelial cell population expressing high levels of Bcl11b and located at the interface between luminal and basal cells. Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Raised by his single mother, Jean, a house cleaner, on Chicago's South Side, Duncan grew up resisting drugs and alcohol, instead concentrating on school. Conversely, a chromosome 1 locus exhibited suggestive linkage to restricted progenitor frequencies but was not linked to HSC frequency. Breast cancers contain a minority population of cancer cells characterized by CD44 expression but low or undetectable levels of CD24 (CD44+CD24-/low) that have higher tumorigenic capacity than other subtypes of cancer cells.We compared the gene-expression profile of CD44+CD24-/low tumorigenic breast-cancer cells with that of normal breast epithelium. Using terminal transferase-mediated dUTP-digoxigenin nick end labeling, we observed apoptotic cells at sites of bcl-xs adenoviral injection. Here we describe two such clones and report that one of them transforms NIH-3T3 cells. 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. Recent observations indicate that, in several types of human cancer, only a phenotypic subset of cancer cells within each tumor is capable of initiating tumor growth. Cells were analyzed by real-time quantitative reverse transcription polymerase chain reaction, single-cell gene expression analysis, flow cytometry, and immunohistochemical, immunoblot, and functional assays. Isobe, T., Zarnegar, M. A., Abdel-Wahab, O., Clarke, M. F. A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer. View details for Web of Science ID 000227329300006. Guinea pig alveolar macrophages were stimulated with opsonized zymosan in the presence of inhibitors of arachidonic acid metabolism: ASA, indomethacin, and ETYA, ASA, at concentrations as high as 60 micrograms/ml, had no effect on either oxygen consumption or superoxide ion formation. Disclosure of potential conflicts of interest is found at the end of this article. View details for DOI 10.1007/s10549-012-2346-4, View details for Web of Science ID 000313201100005, View details for PubMedCentralID PMC3583223. Gene expression analysis of single CD44(+) cells indicated that KIT can promote growth via KITLG autocrine and/or paracrine signaling. Cells that expressed kappa- or lambda-light chains were separated by cell sorting from kappa- or lambda-negative cells and replaced in culture. In normal mouse epithelium, LEFTY1 expression in a subset of luminal cells and rare basal cells opposes BMP7 to promote ductal branching. This conserved requirement for Bmi-1 to promote self-renewal and to repress p16Ink4a expression suggests that a common mechanism regulates the self-renewal and postnatal persistence of diverse types of stem cell. However, the mechanisms regulating p53 subcellular localization remain unclear. Furthermore, in several other nonhematopoietic tissues, cells could be separated into distinct subpopulations with differential Bmi-1 expression. The fragment with a tandem repeat of the 72-bp element also does not associate randomly with histones. Solid tumors arise in organs that contain stem cell populations. Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. One such cDNA clone, KT1, was isolated and its nucleotide sequence was determined. Regulation of normal and cancer stem cell self renewal and senescence by USP16. Michael Clarke is a British academic who specialises in defence studies. Self-renewal requires the integration of survival signals and proliferation controls with the maintenance of an undifferentiated state. He was Director of the Royal United Services Institute from 2007 to 2015. The ability to self-renew is essential for all kinds of stem cells regardless of tissue type. To do so, we used breast tumors of the mouse mammary tumor virus (MMTV)-Wnt-1 mice. Leukemic peripheral blood lymphocytes from individuals infected with the human T-cell leukemia/lymphoma virus (HTLV) were found to express little or no viral RNA before being put into tissue culture. G418-resistant clones, which expressed the c-sis cDNA, were selected and characterized. Notably, these gene sets show similar expression across tissues, differing only in the amplitude and the age of onset of expression. 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. However, inferring both the state and direction of differentiation is challenging. All together, these findings link important stem cell regulators like Bmi1/Usp16 and Cdkn2a to Wnt signaling, and have implications for designing therapies for conditions, like DS, aging or degenerative diseases, where the Wnt pathway is hampered. Individually and in combinations, IL-3, GM-CSF, and Epo were added to the culture medium of LTBMCs that were maintained with 50% medium volume exchange per day. This demands a complex crosstalk between extrinsic signals from the microenvironment and the cell-intrinsic regulators of self-renewal. Thus, the ECMs used did not significantly influence the cell productivity of LTHBMCs. Thus, bcl-2 protects cells from p53-dependent radiation-induced apoptotic cell death and attenuates p53-independent radiation-induced cell death. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. To better understand the molecular basis of radiation-induced cell death, we studied the role of the bcl-2 oncogene and the p53 tumor suppressor gene in this process. These results demonstrate that p16Ink4a/p19Arf and Trp53 have a central role in limiting the expansion potential of multipotent progenitors. Isobe, T., Hisamori, S., Hogan, D. J., Zabala, M., Hendrickson, D. G., Dalerba, P., Cai, S., Scheeren, F., Kuo, A. H., Sikandar, S. S., Lam, J. S., Qian, D., Dirbas, F. M., Somlo, G., Lao, K., Brown, P. O., Clarke, M. F., Shimono, Y. Cell populations of NB cells of onset of expression KIT can promote growth via KITLG autocrine paracrine... 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