Filter By. The calculated molecular weight of RGS18 is 27,610 and the isoelectric point is 8.63. Here, a systematic approach using bioinformatics and array hybridization techniques to analyze gene expression profiles in HSCs is described. Finally, we show evidence that these properties are maintained in the context of an adenoviral vector (AdEHhrk). In 2007, he became the Director of the Royal United Services Institute. We propose the use of this promoter for transcriptional targeting of breast cancer. Following high-dose IR, cell fractionation demonstrated that p53 is induced and targeted to the nucleus. Here, we report that genetic or pharmacologic Hedgehog pathway inhibition intensifies colon inflammation (colitis) in mice. To see if a limited sampling of tumor tissue from human subjects is a feasible way to gather
Purified RGS18 interacts with the alpha subunit of both G(i) and G(q) subfamilies. Thus, the ECMs used did not significantly influence the cell productivity of LTHBMCs. In six of seven tumors examined, Thy1+CD24+ cancer cells, which constituted approximately 1%-4% of tumor cells, were highly enriched for cells capable of regenerating new tumors compared with cells of the tumor that did not fit this profile ("not-Thy1+CD24+"). Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Up to one-third of the long-term culture initiating cell (LTC-IC) are genetically modified by the culture conditions. 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. These data demonstrate that the transcomplementation of replication-deficient adenovirus with exogenous E1 DNA leads to limited replication, and this controlled replication enhances gene transfer efficiency of adenovirus in vivo. To characterize further the function of these two domains, we demonstrate in this report that the previously described major nuclear localization signal works together with Lys(305)-Arg(306) to form a bipartite and functional nuclear localization sequence (NLS) for p53 nuclear import. Dr Michael Clarke is Associate Professor at the National Security College, Crawford School of Public Policy, Australian National University, and Director of the ANU-Indiana University Pan-Asia Institute. While the class is nonetheless challenging, Professor Clark does his best to help all students pass. Since cancers arise as a result of a series of genetic mutations, a better understanding of the consequences of these mutations on the underlying biology of the neoplastic cells will help the development of more effective therapies. Prior to coming to UK, Dr. Clark was the Chief Economist for the Kentucky Legislative Research . His group was the first to discover that the proto-oncogene Bmi-1 regulates stem cell self-renewal via an epigenetic mechanism. Join Facebook to connect with Michael Clarke and others you may know. Amine-derivatized analogues of 1.2 and 3.8 mol of biotin/mol of protein (N1-bGM-CSF and N4-bGM-CSF) and a carboxyl-modified analogue of 4.6 mol of biotin/mol of protein (C5-bGM-CSF) were synthesized. Breast cancer is the most common malignancy in United States women, accounting for >40,000 deaths each year. These results validate the stem cell working model in human CRC and provide a highly robust surface marker profile for CRC stem cell isolation. Gene expression analysis of cells isolated from nonadherent mammospheres revealed overlapping genetic programs with other stem and progenitor cells and identified new markers that may be useful in the identification of mammary stem cells. These data support a model in which low levels of sis gene expression in tumors contribute to the acquisition of some features of transformation but require complementation by other genes or factors to produce a fully malignant phenotype. 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. To further characterize the role of the TWF1 pathway in breast cancer, we found that IL-11 is an important target of TWF1 that regulates breast cancer cell invasion and STAT3 phosphorylation. Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Of five long-term NSGCT survivors, four were treated in first relapse with platinum-sensitive disease. Lobo, N. A., Zabala, M., Qian, D., Clarke, M. F. Serially transplantable mammary epithelial cells express the Thy-1 antigen. Two populations of cells, HSCs and MPP cells, were compared for differential gene expression using microarray analysis. 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. Coexpression of bcl-2 and c-myc can totally overcome p53-induced apoptosis and cell cycle arrest by altering the subcellular trafficking of p53 during the cell cycle: the p53 remains in the cytoplasm of the cotransfected cells during a critical period in G1. From 1990 to 2001 he was the founding Director of the Centre for Defence Studies at King's. Emerging evidence has suggested that the capability of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. Mark Malloch Brown, Baron Malloch-Brown (* 1953), Politiker und stellvertretender Generalsekretr der Vereinten Nationen. A temperature-sensitive mutant of murine p53 (p53Val-135) was transfected by electroporation into murine erythroleukemia cells (DP16-1) lacking endogenous expression of p53. However, multipotent progenitors lack the ability to self-renew, therefore their mitotic capacity and expansion potential are limited and they are destined to eventually stop proliferating after a finite number of cell divisions. Director, Teaching & Learning. Ryan, J. J., Prochownik, E., Gottlieb, C. A., Apel, I. J., Merino, R., Nunez, G., Clarke, M. F. CELL-CYCLE ANALYSIS OF P53-INDUCED CELL-DEATH IN MURINE ERYTHROLEUKEMIA-CELLS. Flow cytometry and microfluidics-based single-cell multiplex RT-PCR allowed dissection of IFN responses in single RV-infected and bystander intestinal epithelial cells (IECs). View details for PubMedCentralID PMC3816928. Chromatin immunoprecipitation (ChIP) is a powerful assay used to probe DNA-protein interactions. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. Transplanted fetal liver and bone marrow cells obtained from Bmi-1-/- mice were able to contribute only transiently to haematopoiesis. Herrema I, Clarke M. Anaesthesia for retinoblastoma screening - a dilemma. The enhanced cytotoxicity was restricted to antibody-coated tumor cells. The coordinated downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells. Loss of Bcl11b leads to a Cdkn2a-dependent exhaustion of ductal epithelium and loss of epithelial cell regenerative capacity. 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. We used a replication-deficient adenoviral vector to transiently overexpress Bcl-xs in MCF-7 human breast cancer cells, which overexpress Bcl-xL. In addition to his clinical duties in the division of Oncology, Dr. Clarke maintains a laboratory focused on two areas of research: i) the control of self-renewal of normal stem cells and their malignant counterparts; and ii) the identification and characterization of cancer stem . M.D., Indiana University (1977) B.A., Indiana University (1973) Contact Academic mfclarke@stanford.edu University - Faculty Department: Med/Stem Cell Position: Assoc Director, Stanford Institute for Stem Cell & Regenerative Medicine Lorry Lokey Stem Cell Building 265 Campus Drive Room G2021A, MC: 5461 Stanford, California 94305 (650) 736-2961 (fax) Investigating mechanisms of cancer stern cell radioresistance. The ability to self-renew is essential for all kinds of stem cells regardless of tissue type. 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. The tumor suppressor protein p53 has been identified as a key regulator of apoptosis in both normal and malignant hematopoietic cells. The development of CSC-targeted treatments will face a number of potential hurdles, including normal stem cell toxicity and the acquisition of treatment resistance, which must be considered in order to maximize the chance that such therapies will be successful. View details for Web of Science ID 000227329300006. At a meeting of the Translation Research Program of the Radiation Therapy Oncology Group held in early 2008, attendees focused on updating the current state of knowledge in cancer stem cell research and discussing ways in which this knowledge can be translated into clinical use across all disease sites. Single-cell RNA sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. C-myb, the normal cellular homolog of the retroviral transforming gene v-myb, encodes a nuclear, transcriptional regulatory protein (p75c-myb). Our studies show that coincident expression of human Bcl-2 protein with p53 prolongs survival of murine erythroleukemia cells. Orthologs of these differentially expressed genes predicted survival of human breast cancer patients from two different study groups. This sequential antibody strategy, combining a tumor-targeting antibody with a second antibody that activates the host innate immune system, may improve the therapeutic effects of antibodies against breast cancer and other HER2-expressing tumors. erenakgun@g.harvard.edu. The mechanism of leukaemogenic transformation by human T-cell leukaemia/lymphoma virus (HTLV), a retrovirus implicated in the aetiology of certain adult T-cell leukaemias and lymphomas, is unknown but is conceivably associated with the expression of the cellular analogues of retroviral oncogenes. In this study, we report that miR-142 efficiently recruits the APC mRNA to an RNA-induced silencing complex, activates the canonical WNT signaling pathway in an APC-suppression dependent manner, and activates the expression of miR-150. Here, we show that human breast tumor biomarker miR-30c regulates invasion by targeting the cytoskeleton network genes encoding twinfilin 1 (TWF1) and vimentin (VIM). These breast tumors are comprised of phenotypically diverse populations of breast cancer cells. Here we implement single-cell PCR gene-expression analysis to dissect the cellular composition of primary human normal colon and colon cancer epithelia. 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. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. These studies suggest that there is a cancer stem cell compartment in the MMTV-Wnt-1 murine breast tumor and that there is a clinical utility of this model for the study of cancer stem cells. He is especially known for his research into the evolution of cooperative breeding in honeyeaters, particularly the genus Manorina and for his work on the response of fauna and flora to wildfire (Clarke 2008, Clarke et al. The Thy-1-CD24medCD49fhigh phenotype contains a rare progenitor population that is able to form primary mammary outgrowths with significantly decreased serial in vivo transplantation potential.CONCLUSIONS: Therefore, Thy-1 expression in the immature cell compartment is a useful tool to study the functional heterogeneity that drives mammary gland development and has implications for disease etiology. Although the existence of mammary stem cells has been suggested by serial transplantation studies in mice, their identification has been hindered by the lack of specific surface markers, and by the absence of suitable in vitro assays for testing stem cell properties: self-renewal and ability to generate differentiated progeny. Zabala, M., Lobo, N. A., Antony, J., Heitink, L. S., Gulati, G. S., Lam, J., Parashurama, N., Sanchez, K., Adorno, M., Sikandar, S. S., Kuo, A. H., Qian, D., Kalisky, T., Sim, S., Li, L., Dirbas, F. M., Somlo, G., Newman, A., Quake, S. R., Clarke, M. F. Clinical and Therapeutic Implications of Cancer Stem Cells. DP16-1 cells which were untransfected or co-transfected with wtp53 and bcl-2 displayed characteristics of cells undergoing necrosis. Many cancers overexpress a member of the bcl-2 family of inhibitors of apoptosis. View details for Web of Science ID 000178717500001. Bockhorn, J., Yee, K., Chang, Y., Prat, A., Huo, D., Nwachukwu, C., Dalton, R., Huang, S., Swanson, K. E., Perou, C. M., Olopade, O. I., Clarke, M. F., Greene, G. L., Liu, H. Innate immune response to homologous rotavirus infection in the small intestinal villous epithelium at single-cell resolution. Differences in self-renewal pathways between normal and malignant stem cells could be targeted by new therapeutic agents to eliminate cancer stem cells. View details for Web of Science ID 000308928300005, View details for Web of Science ID 000318009801791. He was on the senior staff of the S We examined the effect of lower levels of c-sis expression on the phenotype of NIH 3T3 fibroblasts. Thus, the development of proper sampling techniques or improved stem cell retention may be critical to obtain successful long-term cultures. After 5-azacytidine treatment of the cell lines, all cells expressed Ig light chains. Further investigation will reveal whether this translates to improved therapy in the future. KIT knockdown cells had increased expression of enterocyte markers, decreased expression of cycling genes, and, unexpectedly, increased expression of LGR5 associated genes. We demonstrate that radiation-induced cell death occurs by both p53-dependent and -independent pathways and overexpression of bcl-2 modulates both pathways. Michael Clarke Duncan was born on December 10, 1957 in Chicago, Illinois. Lobo, N., Zabala, M., Qian, D., Clarke, M. F. The DLK1-DIO3 imprinted region regulates long-term proliferation in normal and malignant breast epithelium. The weight is in Kilograms- 70 kg. Michael was an assessor on Panel 35 in REF 2014 having been a specialist advisor for the 2008 RAE. We demonstrate that reversing impaired NPC self-renewal via genetic reduction of USP16, a histone modifier and critical physiological antagonist of the Polycomb Repressor Complex 1, can prevent downstream cognitive defects and decrease astrogliosis in vivo. Using this system, we have generated AdEHT2 and AdEHE2F, two conditionally replicative adenoviruses for the treatment of breast cancer. This raises the issue of whether there is a conserved mechanism to effect self-renewing divisions. In addition to clinical duties in oncology, Dr. Clarke maintains a laboratory . Recent evidence suggests that a subset of cancer cells within some tumors, the so-called cancer stem cells, may drive the growth and metastasis of these tumors. 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