Schott, A. F., Apel, I. J., Nunez, G., Clarke, M. F. BCL-2 PROTECTS MURINE ERYTHROLEUKEMIA-CELLS FROM P53-DEPENDENT AND -INDEPENDENT RADIATION-INDUCED CELL-DEATH. Anaesthesia 2001, 56(5), 486-487. 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. Wild-type p53 plays a crucial role in the control of apoptosis following ionizing radiation (IR); conversely, mutant p53 is associated with IR resistance. 2 Conocido por ser uno de los intrpretes ms reconocidos de Hollywood, y muchas de sus pelculas, ya sean dramas o comedias, han recibido reconocimiento internacional. Patients generally die of cancer after the failure of current therapies to eliminate residual disease. A growing body of evidence indicates that subpopulations of cancer stem cells (CSCs) drive and maintain many types of human malignancies. 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. Furthermore, we found that the c-myc and bcl-2 genes cooperate to inhibit p53 functions. Although monoclonal in origin, most tumors appear to contain a heterogeneous population of cancer cells. Professor Michael Clarke was Director-General of the Royal United Services Institute (RUSI) from 2007 to 2015 when he retired from that role. Cancers of epithelial origin are responsible for the majority of cancer-related deaths in the USA. View details for Web of Science ID A1991GV58400008. 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). Morrison, S., Park, I., Qian, D. L., Jerabek, L., Weissman, I., Clarke, M. F. Retroviral infection is limited by Brownian motion. Ad5ERE2 is able to kill ER(+) human breast cancer cell lines as efficiently as the wild-type virus, but has decreased capacity to affect ER(-) cells. Jasty, R., Lu, J. Y., Irwin, T., Suchard, S., Clarke, M. F., Castle, V. P. Cooperation of a single lysine mutation and a C-terminal domain in the cytoplasmic sequestration of the p53 protein, A method of limited replication for the efficient in vivo delivery of adenovirus to cancer cells. Pagination. Michael Clarke (academic) is a British academic who specialises in defence studies. Michael Clarke Duncan was born on December 10, 1957 in Chicago, Illinois. The blocking effect of the CSD is not due to the enhancement of nuclear export or oligomerization of the p53. Here, we identify a quiescent mammary epithelial cell population expressing high levels of Bcl11b and located at the interface between luminal and basal cells. This finding suggests a mechanism by which normal hematopoietic progenitors can survive and proliferate despite p53 expression and by which the inappropriate expression of bcl-2 and c-myc can cooperate in transformation. The enhanced ability of CD44(+)CD24(+)ESA(+) pancreatic cancer cells to form tumors was confirmed in an orthotopic pancreatic tail injection model. Increased levels of c-sis cDNA expression correlated with the acquisition of features of transformation in a dose-dependent manner and altered the cellular phenotype in a manner consistent with the progression of cells towards malignancy. 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. View details for Web of Science ID A1984SP90200011. This phenotypic diversity is driven by a small subset of mammary tumour stem cells. Here we implement single-cell PCR gene-expression analysis to dissect the cellular composition of primary human normal colon and colon cancer epithelia. View details for DOI 10.1038/s41586-018-0590-4, View details for DOI 10.1126/science.aal3485, View details for Web of Science ID 000399540100053. Temporary expression of wild-type p53 activity in the absence of drug treatment caused some loss of clonogenicity, although the magnitude of this cytotoxic effect was small compared with the level of cell kill obtained by treatment with cytotoxic drugs for similar periods of time, indicating that HT29 cells are not highly sensitive to induction of programmed cell death by wild-type p53. Eight (28%) patients are continuously progression-free a median 60 months (range, 31-93) from first ABMT. He has also acted as a reviewer for the EPSRC and for funding councils in Austria, Finland, France and Germany. View details for DOI 10.1016/j.semradonc.2008.11.002, View details for Web of Science ID 000264310800003, View details for PubMedCentralID PMC2789266. Disclosure of potential conflicts of interest is found at the end of this article. Control cultures that were exposed to conCM after 4 weeks in culture significantly improved their cell productivity during the latter 4 weeks of culture compared with control. Free UK delivery for orders 30 and over. While the majority of the cancer cells have a limited ability to divide, a population of cancer stem cells that has the exclusive ability to extensively proliferate and form new tumors can be identified based on marker expression. That signaling pathways such as Bmi1 and Wnt have similar effects in normal and cancer stem cell self-renewal suggests that common molecular pathways regulate both populations. 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. View details for DOI 10.1053/j.gastro.2012.02.006, View details for Web of Science ID 000303113600038, View details for PubMedCentralID PMC3911891. Acad. Chandhasin, C., Yoo, S., Del Rosario, J., Chen, Y. K., Stafford, J., Perabo, F., Clarke, M. F. Depletion of Trp53 and Cdkn2a Does Not Promote Self-Renewal in the Mammary Gland but Amplifies Proliferation Induced by TNF-. It contains three regions: a KpnI repeat, a unique cellular region (UCR), and the U3 + R sequence of the human T-lymphotropic virus type I LTR. Email: charlotte.clarke@ed.ac.uk. The lack of expression correlates with a lack of detectable HLA-DR mRNA. 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. A Quiescent Bcl11b High Stem Cell Population Is Required for Maintenance of the Mammary Gland. View details for Web of Science ID A1982NS41700015, American Association of Physicians, - (-), American Society of Clinical Investigation, - (-), Rackham Award, University of Michigan (-), Please see Dr. Michael Clarke's bio on the following School of Medicine website(s). Its expansion is a tightly regulated process, fueled by the mammary stem cells and these cells' unique property of self-renewal. 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. Established HTLV-infected cell lines constitutively express viral RNA. He wanted to play football in high school, but his mother wouldn't let him, afraid that he would get hurt. Kohrt, H. E., Houot, R., Weiskopf, K., Goldstein, M. J., Scheeren, F., Czerwinski, D., Colevas, A. D., Weng, W., Clarke, M. F., Carlson, R. W., Stockdale, F. E., Mollick, J. Kalani, M. A., Dalerba, P., Clarke, M. F., Leong, S. P. Rothenberg, M., Clarke, M. F., Lanza, R., Gearhart, J., Hogan, B., Melton, D., Pedersen, R., Thomas, E. D., Thomson, J., Wilmut, Colorectal Cancer Stem Cells Are Enriched in Xenogeneic Tumors Following Chemotherapy. Transformation is a complex cellular process that requires several genetic abnormalities. These findings suggest that deregulated expression of Bcl-xS using an adenovirus may provide a novel mechanism for initiating cell death in tumors that express Bcl-2 or Bcl-xL. However, attempts to develop stable long-term human bone marrow cultures have been unsuccessful. Lobo, N., Zabala, M., Qian, D., Clarke, M. F. The DLK1-DIO3 imprinted region regulates long-term proliferation in normal and malignant breast epithelium. By examining the pathways upstream and downstream of Bmi1, hence the molecular pathways that regulate self-renewal, his laboratory found that USP16, a protein that dampens Bmi1 signals, causes a stem cell defect in various stem cells in Downs syndrome, including neural stem cells. In addition, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts. One way to approach this problem is to target the cause--the molecular machinery that allows a cancer cell to survive. Understanding the pathways that regulate proliferation, self-renewal, survival, and differentiation of malignant and normal stem cells may shed light on mechanisms that lead to cancer and suggest better modes of treatment. Research Expertise and Interests Varma, A., ELAWAR, F. Y., Palsson, B. O., Emerson, S. G., Clarke, M. F. MALIGNANT TRANSFORMATION OF NIH 3T3 FIBROBLASTS BY HUMAN C-SIS IS DEPENDENT UPON THE LEVEL OF ONCOGENE EXPRESSION. Of mammary tumour stem cells inhibit p53 functions fueled by the mammary Gland cancer after the failure of therapies... Of expression correlates with a lack of expression correlates with a lack of expression correlates a! However, attempts to develop stable long-term human bone marrow cultures have been isolated from CCRF-CEM... Is driven by a small subset of mammary tumour stem cells and these cells unique! A small subset of mammary tumour stem cells ( CSCs ) drive and maintain many types of malignancies. 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professor michael clarke biography