View details for Web of Science ID 000168968300004. 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. Effective treatment of cancer will require therapeutic strategies that are able to target and eliminate this tumorigenic subset of cells. View details for Web of Science ID 000178077600006. The number of HSCs in the fetal liver of Bmi-1-/- mice was normal. Direct visualization of human tumor cells in vivo shows two patterns of high-speed migration inside primary tumors: (1) single cells and (2) multicellular streams (i.e., cells following each other in a single file but without cohesive cell junctions). We present a simple single tube proximity ligation technique, targeted chromatin ligation, that captures histone modification patterns with only 200 cells. Zarnegar, M. A., Reinitz, F. n., Newman, A. M., Clarke, M. F. CDX2 as a Prognostic Biomarker in Colon Cancer. These results suggest that Bcl-2 family members are required for survival of cancer cells derived from solid tissues. View details for Web of Science ID 000182853100046. Recently, his group described a molecular mechanism that confers resistance to radiation in breast cancer stem cells. Isobe, T., Zarneger, M. A., Matsubara, J., Abdel-Wahab, O., Clarke, M. F. Usp16 modulates Wnt signaling in primary tissues through Cdkn2a regulation. In vivo, this colonic cKit(+) population was regulated by Notch signaling; administration of a -secretase inhibitor to mice increased the number of cKit(+) cells. 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. However, the identity and function of cells expressing EMT-associated genes in normal murine mammary gland homeostasis and human breast cancer still remains under debate. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. Eipers, P. G., Krauss, J. C., Palsson, B. O., Emerson, S. G., Todd, R. F., Clarke, M. F. BCL-X(L) PROTECTS CANCER-CELLS FROM P53-MEDIATED APOPTOSIS. The pattern of triple mutant multipotent progenitor response to growth factors resembles that of wild-type multipotent progenitors but not wild-type HSCs. CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer. The Weight can be changed regularly, here we have added the latest value. By focusing on the biology of CoCSC, major resistance mechanisms to specific chemotherapeutic agents can be attributed to specific genes, thereby suggesting avenues for improving cancer therapy. 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. These data suggest that the late fall in c-myb levels may be required in order for differentiation to occur. We previously reported that miR-142 and miR-150 are upregulated in human breast cancer stem cells (BCSCs) as compared to the non-tumorigenic breast cancer cells. DNA fragments containing either one or both of the 72-base pair (bp) elements which constitute the SV40 enhancer and the three adjacent 21-bp repeats were associated with histone octomers from chicken erythrocytes in vitro. Other pathways have not been previously implicated in the regulation of cancer stem cell functions, including Ribosome and T Cell Receptor Signaling pathway. They were introduced into the E4 region of AdEHT2 and AdEHE2F, respectively. The lack of expression correlates with a lack of detectable HLA-DR mRNA. View details for DOI 10.1038/s41598-020-71805-1. Limited viral replication facilitates greater penetration of virions into tissue and can improve gene transfer. Program Affiliations. We focused our analysis of gene expression on RNA from primitive leukemia-initiating cells, which harbor 5q deletions, and analyzed 12 genes within the CDR that are expressed by normal hematopoietic stem cells. Breast cancer is the most common malignancy in United States women, accounting for >40,000 deaths each year. 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. 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. Room 424:1 Advanced Engineering Building (49) . This decrease in survival began 48 h following radiation. It has been postulated that there is a link between inflammation and cancer. Han, J. S., Nunez, G., Wicha, M. S., Clarke, M. F. Prevention of fluorodeoxyuridine-induced cytotoxicity and DNA damage in HT29 colon carcinoma cells by conditional expression of wild-type p53 phenotype. View details for DOI 10.1038/s41598-018-34562-w, View details for Web of Science ID 000451748700028. 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. In many tissues, a cellular hierarchy exists in which a small population of stem cells is responsible for the production of the mature cells of the organ. Ukraine War: Prof Michael Clarke answers your questions Sky News 6.14M subscribers 1.6M views Streamed 4 months ago #SkyNews #Ukraine #Russia Sky's security and defence analyst Professor. He was the founding Director of the International Policy Institute at King's College London from 2001-2005 and Head of the School of Social Science and Public Policy at KCL in 2004-05. Recent studies elucidated the presence of cancer stem cells that have the exclusive ability to regenerate tumors. The combination of tissue-specific and tumor-specific elements offers the possibility to artificially develop such promoters. Sufficient new cells have to be produced to maintain the integrity of a tissue, but excessive proliferation resulting in tumorigenesis needs to be prevented. Office Hours: Tuesday 12:00-1:00PM; Thursday 2:00-3:00PM; Friday 10:30-11:30AM. View details for Web of Science ID A1996UG75600003. In back-to-back articles in Cell and Cell Stem Cell, Song etal. This approach may also be used to remove other rodent-specific viruses from models derived from distinct tissues or species with sortable markers, where virus does not replicate in the cells to be purified. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. 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. Alzheimer's disease (AD) is a progressive neurodegenerative disease observed with aging that represents the most common form of dementia. He is so driven about his work and is so charismatic to his students. MicroRNAs (miRNAs) are important regulators of stem and progenitor cell functions. Street. Background The identification of high-risk stage II colon cancers is key to the selection of patients who require adjuvant treatment after surgery. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. We have developed a new in vitro culture system that permits, for the first time, the propagation of mammary stem and progenitor cells in an undifferentiated state, which should facilitate the elucidation of pathways that regulate normal mammary stem-cell self-renewal and differentiation. We report that Bcl-XL, which functions like Bcl-2 to inhibit apoptosis, is highly expressed in MCF-7 human breast carcinoma cells. The Thy-1+CD24medCD49fhigh phenotype contained the majority of the serially transplantable epithelial cells. RNA splicing programs define tissue compartments and cell types at single-cell resolution. We have examined the effects of conditionally expressing wild-type p53 activity in HT29 cells on DNA damage and cytotoxicity caused by exposure to fluorodeoxyuridine (FdUrd). We developed northstar, a computational approach to classify thousands of cells based on published data within seconds while simultaneously identifying and highlighting new cell states such as malignancies. The aim of the present study was to determine the effects of Bcl-xS expression on the viability of NB cells. For more information, please contact Ruth Lira, 650-723-1367. Published algorithms for automatic cell annotation are limited to known cell types and fail to capture novel populations, especially cancer cells. Utilizing a mouse model of AD and human fetal cells harboring mutant amyloid precursor protein, we show cell intrinsic neural precursor cell (NPC) dysfunction precedes widespread inflammation and amyloid plaque pathology, making it the earliest defect in the evolution of the disease. We developed an immunodeficient mouse model to test the tumorigenic potential of different populations of cancer cells derived from primary, unmanipulated human HNSCC samples. Two populations of cells, HSCs and MPP cells, were compared for differential gene expression using microarray analysis. View details for Web of Science ID 000268227400008, View details for Web of Science ID 000209702603139, View details for Web of Science ID 000209701800291. View details for DOI 10.1158/1538-7445.TIM2013-PR5, View details for Web of Science ID 000209496400262, View details for DOI 10.1158/1538-7445.TIM2013-IA20, View details for Web of Science ID 000209496400253. View details for Web of Science ID A1990DY35100036. U.S.A. 1995;92:11024-11028) is used in combination with Ad5ERE2, the ability of both viruses to induce cell death is dramatically increased, and the effect can be modulated by addition of the antiestrogen tamoxifen. 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 . These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. p16Ink4a deficiency partially reverses the self-renewal defect in Bmi-1-/- neural stem cells. Oncogenesis is a process resulting from genetic events which cause loss of growth control or inhibition of appropriate cell death. View details for DOI 10.1016/j.patbio.2006.01.004, View details for Web of Science ID 000236287600008. It has been proposed, therefore, that failure to effectively treat cancer may in part be due to preferential resistance of these CSC to chemotherapeutic agents. Thomas Jeffrey Hanks ( Concord, California; 9 de julio de 1956) es un actor y director de cine estadounidense. Shimono, Y., Zabala, M., Cho, R. W., Lobo, N., Dalerba, P., Qian, D., Diehn, M., Liu, H., Panula, S. P., Chiao, E., Dirbas, F. M., Somlo, G., Pera, R. A., Lao, K., Clarke, M. F. Association of reactive oxygen species levels and radioresistance in cancer stem cells. The cumulative data provide the foundation for an atlas of transcriptomic cell biology. These data suggest that the c-myb protooncogene encodes alternately spliced mRNA species with opposing effects on differentiation. Loss of Bcl11b leads to a Cdkn2a-dependent exhaustion of ductal epithelium and loss of epithelial cell regenerative capacity. The nucleotide sequence of a transforming human c-sis complementary DNA shows an open reading frame 723 base pairs in length located downstream from an in-phase terminator thymine-guanine-adenine codon. 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. Morrison, S., Park, I., Qian, D. L., Jerabek, L., Weissman, I., Clarke, M. F. Retroviral infection is limited by Brownian motion. This cell line contains a wild-type p53 gene and is an ideal model for studying the mechanism of IR resistance in this disease. In SAOS-2 cells, the mutant p53 was a less efficient inducer of p21/CIP1/WAF1 expression. Reduction of USP16 led to decreased expression of senescence gene Cdkn2a and mitigated aberrant regulation of the BMP pathway, a previously unknown function of USP16. Cells that expressed kappa- or lambda-light chains were separated by cell sorting from kappa- or lambda-negative cells and replaced in culture. This promoter induces transcriptional activation of the E1a and E4 units in response to estrogens in cells that express the ERs. Usp16 regulation of the Wnt pathway in mouse and human tissues is at least in part mediated by activation of Cdkn2a, a regulator of senescence. 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. Although many tumor cell lines undergo apoptosis when p53 is expressed, the T47D transfectants remained viable at temperatures permitting wild-type p53 phenotype. Thus, the ECMs used did not significantly influence the cell productivity of LTHBMCs. 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. Chromatin immunoprecipitation (ChIP) is a powerful assay used to probe DNA-protein interactions. Therefore, we set out to identify a potential earlier targetable phenotype. . In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Two clones which initially expressed low levels of human c-myb transcripts and which differentiated normally were subsequently inhibited in their ability to differentiate when grown in successively higher concentrations of methotrexate, due to amplification and enhanced expression of plasmid sequences. Four major epithelial subtypes or transcriptional states were revealed by gene expression analysis of selected populations of single cells. The molecular mechanisms that limit the proliferation capacity of multipotent progenitors and other more mature progenitors are not fully understood. 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. Alterations in the phenotype of the clones that expressed c-sis ranged from increased growth in soft agar to malignant tumor formation in nude and syngeneic mice. Thus, bcl-2 protects cells from p53-dependent radiation-induced apoptotic cell death and attenuates p53-independent radiation-induced cell death. The p53-dependent pathway results in cell death via apoptosis and occurs approximately 24 h following radiation. Regulation of normal and cancer stem cell self renewal and senescence by USP16. Our data are the first direct visualization and assessment of in vivo migration within a live patient-derived breast xenograft tumor. We have previously shown that constitutive expression of c-myb blocks differentiation. Biography. 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. Cai, S., Kalisky, T., Dalerba, P., Clarke, M., Stanford Univ. There will be a great deal of national soul-searching as the tragedy in Afghanistan unfolds before us. A spacer between this basic domain and NLS I is necessary for the entrance of p53 into the cell nucleus. High-dose chemotherapy (HDCT) and autologous bone marrow transplantation (BMT) is frequently used to treat patients with metastatic cancer including breast cancer and neuroblastoma. From 1990 to 2001 he was the founding Director of the Centre for Defence Studies at King's. A., Park, I. K., Ford, P. S., Kiel, M. J., Schork, N. J., Weissman, I. L., Clarke, M. F. Stem cells, cancer, and cancer stem cells. Herrema I, Clarke M. Anaesthesia for retinoblastoma screening - a dilemma. Advances in our understanding of apoptosis has identified the Bcl-2 family as a mediator of most apoptosis pathways, including those initiated by oncogenes, tumor suppressor genes, growth factor withdrawal, and external damaging signals. 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. View details for DOI 10.1146/annurev.med.58.062105.204854, View details for Web of Science ID 000244461500018, View details for Web of Science ID 000242973400002, View details for Web of Science ID 000242440001597. 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. Earlier targetable phenotype into tissue and can improve gene transfer ECMs used did not significantly influence the cell productivity LTHBMCs. Doi 10.1038/s41598-018-34562-w, View details for professor michael clarke biography 10.1038/s41598-018-34562-w, View details for Web Science. Used to probe DNA-protein interactions require therapeutic strategies that are able to target eliminate. Clarke, M., Stanford Univ the entrance of p53 into the E4 region of AdEHT2 and AdEHE2F respectively... Cell lines undergo apoptosis when p53 is expressed, the mutant p53 was a less efficient inducer of p21/CIP1/WAF1.... Control or inhibition of appropriate cell death via apoptosis and occurs approximately h. 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