Our results indicate that constitutive expression of a nontruncated human c-myb cDNA can exert profound effects on erythroid differentiation and argue for a causal role of c-myb in the F-MEL differentiation process. These results indicate that a basic domain other than the well defined NLS is required for the nuclear import of p53. From August 1990 to June 1998, 29 males (25 NSGCT) were treated. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. The HUT-102 cell line, derived from a cutaneous T-cell lymphoma and infected with HTLV, expresses several cellular oncogenes. Programmed cell death, or apoptosis, may play an important role in the regulation of hematopoiesis. The theory of cancer stem cells states that a subset of cancer cells within a tumor has the ability to self-renew and differentiate. Who we Are. Under these conditions, the cultures produced as many cells as were inoculated every 2 weeks and led to a greater than 2.5-fold expansion in terms of the number of nonadherent cells produced over a 6- to 8-week period. His best known works are the script he wrote with American film director Stanley Kubrick for 2001: A Space Odyssey (1968) and the novel of that film. Chromatin immunoprecipitation (ChIP) is a powerful assay used to probe DNA-protein interactions. 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. Abnormal p53 cellular localization has been considered to be one of the mechanisms that could inactivate p53 function. 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 . In many cases, breast cancer cells retain the expression of estrogen receptors, and most solid tumors suffer from hypoxia as a consequence of their aberrant vascularization. We will discuss the important implications of this mammary tumour stem-cell model. With the use of subgroup analysis involving independent and retrospective cohorts of patients with stage II or stage III colon cancer, the top candidate gene was tested for its association with disease-free survival and a benefit from adjuvant chemotherapy. Modulation of p53 function is of interest, therefore, both in understanding the control of apoptosis and as a potential therapeutic intervention. Two distinct technical approaches were used for most organs: one approach, microfluidic droplet-based 3'-end counting, enabled the survey of thousands of cells at relatively low coverage, whereas the other, full-length transcript analysis based on fluorescence-activated cell sorting, enabled the characterization of cell types with high sensitivity and coverage. Infection with this vector induced apoptosis in vitro. 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. However, no indomethacin or ETYA inhibition of oxygen utilization was detected in the presence of 1 mM KCN, suggesting that the inhibitable portion of the respiratory burst observed with indomethacin or ETYA was dependent on mitochondrial respiration. Best response after ABMT included: two CR, one CR surgically NED, five PR, three PR surgically NED, seven SD, and eight PD. Hernandez-Alcoceba, R., Pihalja, M., Nunez, G., Clarke, M. F. Molecular cloning and characterization of a novel regulator of G-protein signaling from mouse hematopoietic stem cells. Inhibition of TLR2, its co-receptor CD14, or its downstream targets MYD88 and IRAK1 inhibits growth of human breast cancers in vitro and in vivo. View details for Web of Science ID 000171898900054. We have previously investigated the expression of Bcl-x in neuroblastoma (NB) cell lines and have shown that Bcl-xL is expressed and functions to inhibit chemotherapy-induced apoptosis. His group was the first to discover that the proto-oncogene Bmi-1 regulates stem cell self-renewal via an epigenetic mechanism. 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. The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival. View details for Web of Science ID 000083623000026. 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. Similarly, tumors contain a minority population of cancer stem cells that maintain the tumor. Eighteen relapses occurred a median of 4 months after ABMT I (two late relapses at 28 and 44 months). The arrangement of this clone suggests that its RNA transcript was activated by provirus integration in cis, possibly by the activity of a downstream provirus enhancer. We conclude therefore that the inhibition of oxygen consumption and superoxide production by ETYA at 2 x 10(-5) M is unrelated to inhibition of arachidonic acid metabolism. Here we show that the short half-lives of retroviruses limit the distance that they can effectively travel in solution by Brownian motion, and thus the possibility of successful gene transfer. Upon transfer to 32.5 degrees C, these G1 synchronized cell populations quickly lost viability. Both VIM and TWF1 have been shown to regulate epithelial-to-mesenchymal transition. He was the Director General of the Royal United Services Institute from 2007 to 2015, having previously been Professor of Defence Studies at King's College London since 1995. Rothenberg, M. E., Nusse, Y., Kalisky, T., Lee, J. J., Dalerba, P., Scheeren, F., Lobo, N., Kulkarni, S., Sim, S., Qian, D., Beachy, P. A., Pasricha, P. J., Quake, S. R., Clarke, M. F. Single-cell dissection of transcriptional heterogeneity in human colon tumors. A., Clarke, M. F., Quake, S. R. A single-cell transcriptomic atlas characterizes ageing tissues in the mouse. The CD44(+)CD24(+)ESA(+) pancreatic cancer cells showed the stem cell properties of self-renewal, the ability to produce differentiated progeny, and increased expression of the developmental signaling molecule sonic hedgehog. To understand the regulation of p53 cellular trafficking, we have previously identified two p53 domains involved in its localization. View details for Web of Science ID A1983RE64300046. Additionally, we suggest that constitutive expression of c-myb does not block early commitment events such as activation of histone Hl', subsequent chromatin condensation, and alteration of proliferation-related gene expression. Following release into G1, cells became irreversibly committed to cell death after 4 h at 32.5 degrees C. Commitment to cell death correlated with the first appearance of fragmented DNA. Clarke, M. F., Trainor, C. D., Mann, D. L., Gallo, R. C., Reitz, M. S. TRANSFORMING POTENTIAL OF HUMAN C-SIS NUCLEOTIDE-SEQUENCES ENCODING PLATELET-DERIVED GROWTH-FACTOR. A panel of NB cell lines (CHP-382, GOTO, SHEP-1, SHSY-5Y, and GI-CA-N) were infected with either a bcl-xS adenovirus (pAdRSV-bcl-xS) or a control virus (pAdRSV-lac-z). Hernandez-Alcoceba, R., Pihalja, M., Qian, D. L., Clarke, M. F. Differential gene expression profiling of adult murine hematopoietic stem cells. 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). These data indicate that the simultaneous regulation of E1A and E4 viral transcription units by the appropriate combination of promoters can increase the tumor selectivity of oncolytic adenoviruses. These pathways are commonly repressed in cancer, suggesting a mechanism by which early progenitor cells could gain the ability to self-renew and become malignant with further oncogenic mutations. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. 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. Reitz, M. S., Mann, D., Clarke, M. F., Kalyanaraman, V. S., Robert-Guroff, M., Popovic, M., Gallo, R. C. HOMOLOGY OF HUMAN T-CELL LEUKEMIA-VIRUS ENVELOPE GENE WITH CLASS-I HLA-GENE. Prince, M. E., Sivanandan, R., Kaczorowski, A., Wolf, G. T., Kaplan, M. J., Dalerba, P., Weissman, I. L., Clarke, M. F., Ailles, L. E. Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Office Hours: Tuesday 12:00-1:00PM; Thursday 2:00-3:00PM; Friday 10:30-11:30AM. We examined such heterogeneity in the small intestine during rotavirus (RV) infection. Oncogenesis is a process resulting from genetic events which cause loss of growth control or inhibition of appropriate cell death. F-MEL clones expressing the highest levels of the human c-myb mRNA differentiate poorly in response to dimethyl sulfoxide. View details for DOI 10.1016/j.gde.2008.01.017, View details for Web of Science ID 000256954100008, View details for Web of Science ID 000253701800002, View details for Web of Science ID 000258805300065, View details for Web of Science ID 000251969000893. Heights. These results indicated the involvement of cis-acting sequences in the regulation of p53 subcellular localization. The Bcl-2 protein inhibits apoptosis induced by a variety of signals, in a range of cell types and in diverse organisms, and it is implicated in both normal development and oncogenesis. Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy. We show that human colon cancer tissues contain distinct cell populations whose transcriptional identities mirror those of the different cellular lineages of normal colon. Associate Professor of Instruction; PhD. The enhanced ability of CD44(+)CD24(+)ESA(+) pancreatic cancer cells to form tumors was confirmed in an orthotopic pancreatic tail injection model. Emerson, S. G., Palsson, B. O., Clarke, M. F. INFLUENCE OF MEDIUM EXCHANGE SCHEDULES ON METABOLIC, GROWTH, AND GM-CSF SECRETION RATES OF GENETICALLY ENGINEERED NIH-3T3 CELLS. Sikandar, S. S., Kuo, A. H., Kalisky, T. n., Cai, S. n., Zabala, M. n., Hsieh, R. W., Lobo, N. A., Scheeren, F. A., Sim, S. n., Qian, D. n., Dirbas, F. M., Somlo, G. n., Quake, S. R., Clarke, M. F. 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