Here, we have shown that upon encountering trastuzumab-coated, HER2-overexpressing breast cancer cells, human NK cells become activated and express the costimulatory receptor CD137. A large number of genes that were differentially expressed by enriched populations of HSCs and MPP cells were identified. Professor Michael Clarke, a prominent military analyst, told Express.co.uk that Ukraine could use Britain's Challenger 2 tanks to split the combat frontline and "isolate Crimea". He is so driven about his work and is so charismatic to his students. miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway. View details for DOI 10.1038/s41586-020-2496-1, View details for Web of Science ID 000485326200019, View details for DOI 10.1158/1538-7445.SABCS18-SY17-02, View details for Web of Science ID 000488129901140, View details for Web of Science ID 000453773601250. The telomerase core promoter failed to block the replication of the virus in telomerase-negative cells. Data on sequence comparisons with mouse and chicken homologues of c-myb coupled with oligonucleotide hybridization to genomic clones of the human c-myb gene indicate that this alternative splicing process utilizes three closely spaced splice donor sites and two unique exons present between viral defined exons 5 and 6. Unfortunately, although chemotherapy and/or radiation therapy can sometimes shrink tumors, metastatic cancers of epithelial origin are essentially incurable. Dalerba, P., Sahoo, D., Paik, S., Guo, X., Yothers, G., Song, N., Wilcox-Fogel, N., Forg, E., Rajendran, P. S., Miranda, S. P., Hisamori, S., Hutchison, J., Kalisky, T., Qian, D., Wolmark, N., Fisher, G. A., van de Rijn, M., Clarke, M. F. A cell-intrinsic role for TLR2-MYD88 in intestinal and breast epithelia and oncogenesis. View details for PubMedCentralID PMC5698470. Thus, these mice allow for the isolation of viable Bmi-1-expressing cells and have the potential to become a useful tool for understanding the role of Bmi-1 in normal and cancer stem cells in multiple tissue types. Unequivocal proof that stem cells exist in the haematopoietic system has given way to the prospective isolation of several tissue-specific stem and progenitor cells, the initial delineation of their properties and expressed genetic programmes, and the beginnings of their utility in regenerative medicine. We report that Bcl-XL, which functions like Bcl-2 to inhibit apoptosis, is highly expressed in MCF-7 human breast carcinoma cells. There will be a great deal of national soul-searching as the tragedy in Afghanistan unfolds before us. Pardal, R., Clarke, M. F., Morrison, S. J. A., Ozawa, M. G., Silva, O., Toland, A., Vemuri, V. N., Afik, S., Awayan, K., Bierman, R., Botvinnik, O. The tight regulation of E1A expression correlated with the ability of these viruses to replicate and kill human cancer cells that express estrogen receptors, or are maintained under hypoxic conditions. Two cDNA clones of the human c-myb gene have been isolated from a CCRF-CEM leukemia cell cDNA library and sequenced in their entirety. In addition, through targeting the cancer stem cell and its dysregulated self-renewal, our therapies for treating cancer are likely to improve. View details for Web of Science ID A1991FC72500007. Furthermore, we propose a model in which transformation of stem cells, or early progenitor cells, results in carcinogenesis. 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. 29 Oxford St, Pierce 229. jaiz@seas.harvard.edu (617) 495-3558. Lobo, N. A., Zabala, M., Qian, D., Clarke, M. F. Serially transplantable mammary epithelial cells express the Thy-1 antigen. Liu, R., Wang, X., Chen, G. Y., Dalerba, P., Gurney, A., Hoey, T., Sherlock, G., Lewicki, J., Shedden, K., Clarke, M. F. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Here we show that Bmi-1 is required for the self-renewal of stem cells in the peripheral and central nervous systems but not for their survival or differentiation. Epithelial-to-mesenchymal transition has been shown to correlate with therapy resistance, but the functional link and signalling pathways remain to be elucidated. B., Byrne, A., Chen, M., Dehghannasiri, R., Gayoso, A., Granados, A. The pattern of triple mutant multipotent progenitor response to growth factors resembles that of wild-type multipotent progenitors but not wild-type HSCs. KIT Signaling Promotes Growth of Colon Xenograft Tumors in Mice and Is Up-Regulated in a Subset of Human Colon Cancers. Wu, A. R., Neff, N. F., Kalisky, T., Dalerba, P., Treutlein, B., Rothenberg, M. E., Mburu, F. M., Mantalas, G. L., Sim, S., Clarke, M. F., Quake, S. R. Oncogenic miRNAs and the perils of losing control of a stem cell's epigenetic identity. Finally we report that the TNF-NFKB1 signalling pathway directly regulates CD47 by interacting with a constituent enhancer located within a CD47-associated SE specific to breast cancer. 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. The inhibitory effect on F-MEL differentiation appeared to be independent of the early decline in c-myc transcripts which were normally regulated in all cases examined. This raises the issue of whether there is a conserved mechanism to effect self-renewing divisions. Weber, B. L., Westin, E. H., Clarke, M. F. ALTERNATIVE SPLICING OF THE HUMAN C-MYB GENE. View details for DOI 10.1371/journal.pone.0002428, View details for Web of Science ID 000263280700013, View details for PubMedCentralID PMC2413402, View details for Web of Science ID 000454834700190. Cell types of origin of the cell-free transcriptome. We have developed an in vitro cultivation system that allows for propagation of human mammary epithelial cells (HMECs) in an undifferentiated state, based on their ability to proliferate in suspension, as nonadherent mammospheres. Through this property, striking parallels can be found between stem cells and cancer cells: tumours may often originate from the transformation of normal stem cells, similar signalling pathways may regulate self-renewal in stem cells and cancer cells, and cancer cells may include 'cancer stem cells' - rare cells with indefinite potential for self-renewal that drive tumorigenesis. Clarke, M. F., Gelmann, E. P., Reitz, M. S. RELATION OF RESPIRATORY BURST AND ARACHIDONATE METABOLISM DURING PHAGOCYTOSIS BY GUINEA-PIG ALVEOLAR MACROPHAGES. CLARKE Michael Function : Distinguished Fellow, Royal United Services Institute (RUSI) Political Committee, Saturday 12 October Biography Professor Michael Clarke was Director General of the Royal United Services Institute from 2007-2015, where he remains a Distinguished Fellow. A., Jones, R. C., Nicolis di Robilant, B. n., Nong, R. Y., Norton, J. View details for Web of Science ID A1983RE64300046. View details for DOI 10.1073/pnas.1006732107, View details for Web of Science ID 000283184800050, View details for PubMedCentralID PMC2964232. View details for Web of Science ID A1995RP92400014. Prior to that he was Professor of Defence Studies at King's College London, and Deputy Vice-Principal for Research Development. View details for DOI 10.1038/s41587-021-01188-9, View details for DOI 10.7554/eLife.70692.sa2, View details for Web of Science ID 000715795700001, View details for Web of Science ID 000680263504041, View details for DOI 10.1200/JCO.2021.39.15_suppl.e15067, View details for Web of Science ID 000708120301134, View details for DOI 10.1200/JCO.2021.39.15_suppl.3105, View details for Web of Science ID 000708120601279. Clinical and Therapeutic Implications of Cancer Stem Cells Reply, Solid tumor cancer stem cells: From bench to bedside, ASXL1 regulates cellular differentiation and initiates tumorigenesis in colon. Park, I. K., Qian, D. L., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., Morrison, S. J., Clarke, M. F. Prospective identification of tumorigenic breast cancer cells. Previous studies have shown that blocking DLL4 signaling reduced tumor growth by disrupting productive angiogenesis. In 2007, he became the Director of the Royal United Services Institute. Transformed mammary stem or progenitor cells undergo aberrant differentiation processes that result in generation of the phenotypic heterogeneity found in human and rodent breast cancers. The retrovirus transduced culture continued to produce genetically modified hematopoietic progenitors for up to 6 weeks, the duration of the culture period. Gene profiling experiments have revealed similarities between cancer and embryonic stem (ES) cells. In mammary glands, reduced levels of Usp16 increase tissue responsiveness to Wnt, resulting in upregulation of the downstream Wnt target Axin2, expansion of the basal compartment and increased in vitro and in vivo epithelial regeneration. Previous groups have shown that CD24medCD49fhigh cells enriched for long-lived mammary epithelial cells can be serially transplanted.METHODS: Flow cytometry-based enrichment of distinct phenotypic populations was assessed for their gene expression profiles and functional proliferative attributes in vitro and in vivo.RESULTS: Here, we show Thy-1 is differentially expressed in the CD24medCD49fhigh population, which allowed us to discern two functionally different populations. Thus, bcl-2 protects cells from p53-dependent radiation-induced apoptotic cell death and attenuates p53-independent radiation-induced cell death. This is an overview of the elements and molecules involved in p53 nucleocytoplasmic transportation. The human RGS18 ortholog has a tissue-specific expression pattern similar to that of mouse RGS18. One such cDNA clone, KT1, was isolated and its nucleotide sequence was determined. To evaluate the feasibility of positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) in patients with germ cell tumor (GCT) to monitor treatment and differentiate residual masses after chemotherapy.Twenty-six FDG PET studies were performed in 21 patients with GCT, FDG uptake of tumors was interpreted visually, and the lean standardized uptake value (SUVlean) was determined. Program Affiliations. Morrison, S. J., Qian, D., Jerabek, L., Thiel, B. Cai, S., Kalisky, T., Sahoo, D., Dalerba, P., Feng, W., Lin, Y., Qian, D., Kong, A., Yu, J., Wang, F., Chen, E. Y., Scheeren, F. A., Kuo, A. H., Sikandar, S. S., Hisamori, S., van Weele, L. J., Heiser, D., Sim, S., Lam, J., Quake, S., Clarke, M. F. Targeted chromatin ligation, a robust epigenetic profiling technique for small cell numbers. Lower concentrations of ETYA (5 x 10(-6) M), which had no effect on the respiratory burst of phagocytosing alveolar macrophages, also inhibited arachidonic acid metabolism. In this episode, Eliot Wilson talks to Professor Michael Clarke, former head of the Royal United Services Institute, about the UK's Integrated Review and how far it represents a break from traditional thinking on our place in the world. Michael Clarke, defence analyst: Yes, the Black Sea is international and a UK warship went in there to Ukraine when the QE carrier was on its world tour last year. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. In this issue of Cell Stem Cell, Hermann et al. The CSD could block the binding of p53 to the NLS receptor, importin alpha, and reduce the efficiency of p53 nuclear import in MCF-7, H1299, and Saos-2 cells. View details for DOI 10.1016/j.gde.2003.11.007, View details for Web of Science ID 000188978200008. View details for Web of Science ID 000173193700014. Microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice. Join Facebook to connect with Michael Clarke and others you may know. 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. We show that human colon cancer tissues contain distinct cell populations whose transcriptional identities mirror those of the different cellular lineages of normal colon. Cancers originally develop from normal cells that gain the ability to proliferate aberrantly and eventually turn malignant. In concert with endogenous DMSO-induced globin transcription during MEL cell differentiation, the beta-globin c-myb transcription unit of the transfected plasmid is activated after 3-5 days of culture in media containing DMSO. Here we implement single-cell PCR gene-expression analysis to dissect the cellular composition of primary human normal colon and colon cancer epithelia. It was found that a single mutation of Arg-306 resulted in the defect of p53 nuclear import. Michael Clarke Duncan was born on December 10, 1957 in Chicago, Illinois. This problem can be addressed by allowing limited viral replication. Adorno, M., di Robilant, B. N., Sikandar, S. S., Acosta, V. H., Antony, J., Heller, C. H., Clarke, M. F. Usp16 modulates Wnt signaling in primary tissues through Cdkn2a regulation. Kim et al. Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. View details for Web of Science ID A1991GR93700016. Using a model in which human breast cancer cells were grown in immunocompromised mice, we found that only a minority of breast cancer cells had the ability to form new tumors. After 48 h in culture, DR antigen expression was substantially increased, but no significant changes were observed in methylation of the DR alpha locus or in the amount of DR mRNA which was present. Parks, I. K., Klug, C. A., Li, K. J., Jerabek, L., Li, L. H., Nanamori, M., Neubig, R. R., Hood, L., Weissman, I. L., Clarke, M. F. A novel, conditionally replicative adenovirus for the treatment of breast cancer that allows controlled replication of E1a-deleted adenoviral vectors. Al-Hajj, M., Becker, M. W., Wichal, M., Weissman, I., Clarke, M. F. Bmi1, stem cells, and senescence regulation. 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. View details for DOI 10.1016/j.jcmgh.2017.01.006. Up to one-third of the long-term culture initiating cell (LTC-IC) are genetically modified by the culture conditions. Li, C., Heidt, D. G., Dalerba, P., Burant, C. F., Zhang, L., Adsay, V., Wicha, M., Clarke, M. F., Simeone, D. M. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Schaum, N. n., Lehallier, B. n., Hahn, O. n., Plovics, R. n., Hosseinzadeh, S. n., Lee, S. E., Sit, R. n., Lee, D. P., Losada, P. M., Zardeneta, M. E., Fehlmann, T. n., Webber, J. T., McGeever, A. n., Calcuttawala, K. n., Zhang, H. n., Berdnik, D. n., Mathur, V. n., Tan, W. n., Zee, A. n., Tan, M. n., Pisco, A. O., Karkanias, J. n., Neff, N. F., Keller, A. n., Darmanis, S. n., Quake, S. R., Wyss-Coray, T. n. Northstar enables automatic classification of known and novel cell types from tumor samples. These advances in BCSC imaging revealed that CD44(+) cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. View details for DOI 10.1073/pnas.0610117104, View details for Web of Science ID 000243761100053. Together, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity. View details for Web of Science ID 000316614600063. Professor Clark is someone that should teach all students. Using a xenograft model in which primary human pancreatic adenocarcinomas were grown in immunocompromised mice, we identified a highly tumorigenic subpopulation of pancreatic cancer cells expressing the cell surface markers CD44, CD24, and epithelial-specific antigen (ESA). 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