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-. View details for Web of Science ID 000178077600006. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy. In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. 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. View details for Web of Science ID A1983RE64300046. View details for DOI 10.1016/j.stem.2007.08.012, View details for Web of Science ID 000251055200003. 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). (2010) dissect the gene expression signature of ES cells into three functional modules and find that the Myc module, including genes targeted by Myc-interacting proteins, accounts for most of the similarity between ES and cancer cells. 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. Mark Malloch Brown, Baron Malloch-Brown (* 1953), Politiker und stellvertretender Generalsekretr der Vereinten Nationen. identify miR-22 as both a repressor of TET proteins and a powerful oncogene in the mammary epithelium and hematopoietic system. View details for Web of Science ID 000301021500029, View details for PubMedCentralID PMC3287235. In patients with colorectal cancer (CRC) that metastasizesto the liver, there are several key goals for improving outcomes including early detection, effective prognostic indicators of treatment response, and accurate identification of patients at high risk for recurrence. He had office hours every day and heavily cared for your well-being. 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 cells. Bcl11b(high) cells are enriched for cells that can regenerate mammary glands in secondary transplants. Han, J. S., Qian, D. L., Wicha, M. S., Clarke, M. F. Targeting cancer cell death with a bcl-x(s) adenovirus. Furthermore, the tumorigenic CD44(+) cells differentially express the BMI1 gene, at both the RNA and protein levels. Recently, we have found that a recombinant adenovirus vector that contains a bcl-x, minigene (a dominant negative inhibitor of the bcl-2 family), called the bcl-x(s) adenovirus, is lethal to cancer cells derived from epithelial tissues, but not to normal human hematopoietic cells. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance. To delineate more accurately the point at which Myb blocks differentiation, MEL cells were transfected with a human c-myb construct under the control of the beta-globin promoter and enhancers. In addition, wild-type p53 expression also prevented FdUrd-induced DNA double-strand breaks and, unexpectedly, single-strand breaks in parental (mature) DNA. The HUT-102 cell line, derived from a cutaneous T-cell lymphoma and infected with HTLV, expresses several cellular oncogenes. The Shep-1 neuroblastoma cell line is highly resistant to IR. Automated microfluidic chromatin immunoprecipitation from 2,000 cells. Programmed cell death (PCD) plays an important role in normal and malignant hematopoieis. We therefore propose to initiate a phase I clinical trial to test the safety of this virus in women with breast cancer undergoing high does chemotherapy and autologous BMT. View details for Web of Science ID A1995RY96700021. Evidence from studies in murine and human embryonic stem cells indicates that Polycomb group proteins play a dynamic role in concert with master transcriptional regulators in actively maintaining an undifferentiated state, suggesting that this mechanism applies to multiple types of stem cell. The tumor suppressor protein p53 has been identified as a key regulator of apoptosis in both normal and malignant hematopoietic cells. Therefore, we set out to identify a potential earlier targetable phenotype. Hematopoietic stem cells (HSCs) have self-renewal capacity and multilineage developmental potentials. This new paradigm of oncogenesis has been validated in a growing list of tumors. View details for PubMedCentralID PMC5698470. To enrich mRNAs predominantly expressed in uncommitted cell lineages, 54 000 cDNA clones generated from a highly enriched population of HSCs and a mixed population of stem and early multipotent progenitor (MPP) cells were arrayed on nylon membranes (macroarray or high-density array), and subtracted with cDNA probes derived from mature lineage cells including spleen, thymus, and bone marrow. Pardal, R., Clarke, M. F., Morrison, S. J. GSE professors bring the latest advances in the social sciences, technology and teacher preparation to the field of education. Professor Michael Clarke was Director General of the Royal United Services Institute (RUSI) from 2007 to 2015. Down's syndrome results from full or partial trisomy of chromosome 21. The median PFS and OS for the whole group are 4 and 14 months, respectively. Prof Mike Clarke is Professor of Zoology at La Trobe University. Adjunct Senior Lecturer Dr Urs Wermuth. Cho, R. W., Wang, X., Diehn, M., Shedden, K., Chen, G. Y., Sherlock, G., Gurney, A., Lewicki, J., Clarke, M. F. What can we learn about breast cancer from stem cells? Transient overexpression of RGS18 attenuated inositol phosphates production via angiotensin receptor and transcriptional activation through cAMP-responsive element via M1 muscarinic receptor. 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 wild-type p53/GFP fusion protein was localized in the cytoplasm, the nucleus, or both compartments in a subset of the cells. Patients who do poorly despite ABMT have a mediastinal primary site, true cisplatin-refractory disease, disease progression prior to ABMT, and/or markedly elevated betaHCG at ABMT. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Since only a portion of the cells in culture expressed Ig light chains, experiments were carried out to exclude the possibility that the cultures were not a mixture of B and T or non-B cells. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. Four major epithelial subtypes or transcriptional states were revealed by gene expression analysis of selected populations of single cells. View details for DOI 10.1186/s13058-018-1006-y, View details for Web of Science ID 000447203300001, View details for Web of Science ID 000440602000145, View details for Web of Science ID 000440602000051, View details for DOI 10.1200/JCO.2018.36.4_suppl.683, View details for Web of Science ID 000436174100659. Following his specialty training in medical oncology at Royal Prince Alfred and Westmead Hospitals, Professor Boyer was a Research Fellow and Clinical Fellow at the Ontario Cancer Institute and Princess Margaret Hospital in Toronto, Canada, where he completed his PhD on cell biology. These data represent a new resource for cell biology, reveal gene expression in poorly characterized cell populations and enable the direct and controlled comparison of gene expression in cell types that are shared between tissues, such as T lymphocytes and endothelial cells from different anatomical locations. Furthermore, we found that the c-myc and bcl-2 genes cooperate to inhibit p53 functions. When a promoter containing these elements is used to control the expression of the pro-apoptotic gene harakiri, the induction of cell death can be activated by estrogens and hypoxia, and inhibited by antiestrogens such as tamoxifen. To determine the mechanism, by which this virus spares normal hematopoietic cells, we isolated normal mouse hematopoietic stem cells and infected them with an adenovirus that contains a beta-galactosidase minigene. We compared commercially available single-cell RNA amplification methods with both microliter and nanoliter volumes, using sequence from bulk total RNA and multiplexed quantitative PCR as benchmarks to systematically evaluate the sensitivity and accuracy of various single-cell RNA-seq approaches. Cancer stem cells are a minor population of tumor cells that possess the stem cell property of self-renewal. This decrease in survival began 48 h following radiation. Morrison, S. J., Qian, D., Jerabek, L., Thiel, B. Finally, the laboratory is actively pursuing how cancer stem cells self-renew to maintain themselves and escape the genetic constraints on unlimited self-renewal that regulate normal stem cell numbers. Liu, H., Qian, D., Lin, J., Lobo, N., Zhang, H., Dalerba, P., Shimono, Y., Diehn, M., Jeffrey, S., Clarke, M. Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors. Abnormal p53 cellular localization has been considered to be one of the mechanisms that could inactivate p53 function. View details for DOI 10.1016/j.jcmgh.2017.01.006. 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. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. View details for DOI 10.1073/pnas.1121623109, View details for DOI 10.1158/1538-7445.AM2012-3331, View details for Web of Science ID 000209701505088, View details for DOI 10.1158/1538-7445.AM2012-1012, View details for Web of Science ID 000209701505194. Dalerba, P., Sahoo, D., Paik, S., Guo, X., Yothers, G., Song, N., Wilcox-Fogel, N., Forgo, 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. CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer. We present a simple single tube proximity ligation technique, targeted chromatin ligation, that captures histone modification patterns with only 200 cells. A., Sim, S., Okamoto, J., Johnston, D. M., Qian, D., Zabala, M., Bueno, J., Neff, N. F., Wang, J., Shelton, A. Resultant tumors had a phenotypic diversity similar to that of the original tumor and behaved in a similar manner when passaged. For more information, please contact Ruth Lira, 650-723-1367. miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway. We review the biological basis and the therapeutic implications of the stem cell model of cancer. Dylla, S. J., Beviglia, L., Park, I., Chartier, C., Raval, J., Ngan, L., Pickell, K., Aguilar, J., Lazetic, S., Smith-Berdan, S., Clarke, M. F., Hoey, T., Lewicki, J., Gurney, A. L. Characterizing metastatic cancer stem cells from human breast cancer. Knockdown of endogenous miR-142 effectively suppressed organoid formation by BCSCs and slowed tumor growth initiated by human BCSCs in vivo. The mammary epithelium undergoes several rounds of extensive proliferation during the female reproductive cycle. (Funded by the National Comprehensive Cancer Network, the National Institutes of Health, and others.). Professor Clarke has over 45 years of professional experience with approximately 250 publications and presentations. Professor Clarke was presented by Professor Len Scott from the Department of International Politics. An in vivo reconstitution assay revealed that the frequency of HSCs was 1/16 in Bmi-1high c-kit+ lin -Sca-1+ bone marrow (BM) cells and 1/49 in Bmi-1 high lin- BM cells, suggesting that Bmi-1 may serve as a marker for normal HSCs. The induced p53 is functional as p53-responsive genes (Waf-1 and MDM-2) are appropriately induced following IR. Orhan Eren Akgun. A., Parmiani, G., Castelli, C., Clarke, M. F. Identification of pancreatic cancer stem cells. Dr. Michael F. Clarke is the Associate Director of the Stanford Institute for Stem Cell and Regenerative Medicine. In addition to his clinical duties in the division of Oncology, Dr . Several pathways, including Wnt signaling, MAP Kinase signaling, and Adherens Junction, are well known for their role in cancer development and stem cell biology. View details for Web of Science ID A1984SJ97500057. We have designed a microfluidic device to perform sensitive ChIP analysis on low cell numbers in a rapid, automated fashion while preserving the specificity of the assay. Although neither the visual interpretation nor SUVlean differentiated mature teratoma from necrosis or scar, there were statistically significant differences in the kinetic rate constants K1 and K between mature teratoma and necrosis or scar as follows: K1, 0.113 mL/min/g +/- 0.026 versus 0.036 mL/min/g +/- 0.005 (P < .05); K, 0.005 mL/min/g +/- 0.003 versus 0.0008 mL/min/g +/- 0.0001 (P < .05).FDG PET with kinetic analysis appears to be a promising method for management of disease in patients with GCT after treatment. , sex, and others. ) at La Trobe University 10.1038/s41586-018-0590-4, details. 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