It is clear that new approaches are needed to treat these diseases. 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. The Bcl-XL protein is a recently discovered member of the bcl-2 family which has been shown to protect cells from some forms of programmed cell death, but has not yet been implicated in the genesis of human carcinomas. Mann, D. L., Clark, J., Clarke, M., Reitz, M., Popovic, M., Franchini, G., Trainor, C. D., STRONG, D. M., Blattner, W. A., Gallo, R. C. Presence of HTLV in a subset of T cells from an infected patient: some immunochemical properties of the infected cells. 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. Inhibiting USP16 rescues stem cell aging and memory in an Alzheimer's model. View details for DOI 10.1016/j.gde.2003.11.007, View details for Web of Science ID 000188978200008. 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. 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) View details for Web of Science ID A1992KX78000004. Further study with ETYA showed that the inhibitor at 2 x 10(-5) M had little effect on uptake of 125I-labeled zymosan but did abolish the conversion of 14C-arachidonic acid to a compound that co-migrated with authentic 12-HETE on silica gel plates. This suggests RGS18 can act on G(q)-mediated signaling pathways in vivo. Michael Clarke is a British academic who specialises in defence studies. Here we developed a CSC model for the study of human colorectal cancer (CRC). Guinea pig alveolar macrophages were stimulated with opsonized zymosan in the presence of inhibitors of arachidonic acid metabolism: ASA, indomethacin, and ETYA, ASA, at concentrations as high as 60 micrograms/ml, had no effect on either oxygen consumption or superoxide ion formation. View details for Web of Science ID A1994PC47400008. Interest in single-cell whole-transcriptome analysis is growing rapidly, especially for profiling rare or heterogeneous populations of cells. Growing evidence suggests that pathways that regulate the self-renewal of normal stem cells are deregulated in cancer stem cells resulting in the continuous expansion of self-renewing cancer cells and tumor formation. Email: charlotte.clarke@ed.ac.uk. Ageing is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death1. Our results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs. We also discuss thelatest advances to maximize regional and systemic therapies aimed at decreasing intrahepatic recurrence, review recent insights into the tumor microenvironment, and summarize advances in noninvasive multimodal biomarkers for early detection of primary and recurrent disease. Patients with relapsed/ refractory testicular cancer benefit most from ABMT if they have platinum-sensitive disease in first relapse. In the colon, cKit(+) goblet cells were interdigitated with Lgr5(+) stem cells. Using an ELISA assay which quantitates DNA damage, we demonstrate that this sensitization is due to apoptosis, suggesting the therapeutic utility of targeting this pathway. Although data have been provided to support this theory in human blood, brain, and breast cancers, the identity of pancreatic cancer stem cells has not been determined. 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. Although monoclonal in origin, most tumors appear to contain a heterogeneous population of cancer cells. Some mice were given the RTK inhibitor imatinib after injection of cancer cells; tumor growth was measured based on bioluminescence. Uncultured peripheral blood T-cells from human T-cell leukemia-lymphoma virus-infected individuals expressed DR antigens at a low level, and the DR alpha locus was partially unmethylated. The Bcl-2 family of proteins: regulators of cell death and survival. View details for DOI 10.1016/j.stem.2016.11.007, View details for PubMedCentralID PMC5341693. Here, we report a mouse model that, in the absence of p53 and the presence of oncogenic KrasG12D , develops breast tumors. 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. In this report, we analyzed the possible existence of cis-acting sequences involved in intracellular trafficking of the p53 protein. The DR alpha genes in both cell lines are hypermethylated relative to the same genes in T-cell lines infected with human T-cell leukemia virus (HTLV) and derived from patients with adult T-cell leukemia/lymphoma (ATL). Sen, A., Rothenberg, M. E., Mukherjee, G., Feng, N., Kalisky, T., Nair, N., Johnstone, I. M., Clarke, M. F., Greenberg, H. B. Remodeling of Endogenous Mammary Epithelium by Breast Cancer Stem Cells. 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. Interestingly, phytohemagglutin-stimulated leukocyte-conditioned medium stimulated LTHMBCs in a similar fashion, as did conditioned medium from early LTHBMCs. Bcl11b(high) cells are enriched for cells that can regenerate mammary glands in secondary transplants. Woodward, W. A., Bristow, R. G., Clarke, M. F., Coppes, R. P., Cristofanilli, M., Duda, D. G., Fike, J. R., Hambardzumyan, D., Hill, R. P., Jordan, C. T., Milas, L., Pajonk, F., Curran, W. J., Dicker, A. P., Chen, Y. [1] Clarke is a former Deputy Vice-Principal and Director of Research Development at King's College London, where he remains a Visiting Professor of Defence Studies. Most importantly, miR-200c strongly suppressed the ability of normal mammary stem cells to form mammary ducts and tumor formation driven by human BCSCs in vivo. We define cell type signature scores, which allow the inference of cell types that contribute to cell-free RNA for a variety of diseases. Professor Michael Clarke, a prominent military analyst, told Express.co.uk that Ukraine could use Britain's Challenger 2 tanks to split the combat frontline and "isolate Crimea". 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. This development may play an important role in realizing human gene therapy. We reveal linear and nonlinear shifts in gene expression during ageing, with the associated genes clustered in consistent trajectory groups with coherent biological functions-including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Wu, A. R., Neff, N. F., Kalisky, T., Dalerba, P., Treutlein, B., Rothenberg, M. E., Mburu, F. M., Mantalas, G. L., Sim, S., Clarke, M. F., Quake, S. R. Oncogenic miRNAs and the perils of losing control of a stem cell's epigenetic identity. Wu, A. R., Hiatt, J. erenakgun@g.harvard.edu. Nuovo ateismo o neo-ateismo, anche nella grafia neoateismo (in inglese New Atheism), una corrente di pensiero che raccoglie le posizioni promosse da alcuni atei del XXI secolo. He wanted to play football in high school, but his mother wouldn't let him, afraid that he would get hurt. Major conclusions of the symposium were that the flow cytometry of multiple markers in fresh tissue would remain the standard technique of evaluating cancer-initiating cells and that surrogates need to be developed for both experimental and clinical use. View details for DOI 10.1016/j.stem.2009.05.019, View details for Web of Science ID 000269511900010. In one clone, the alternative splicing would generate a predicted myb protein with a three amino acid deletion in the region involved in transcription activation. 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. Diehn, M., Cho, R. W., Lobo, N. A., Kalisky, T., Dorie, M. J., Kulp, A. N., Qian, D., Lam, J. S., Ailles, L. E., Wong, M., Joshua, B., Kaplan, M. J., Wapnir, I., Dirbas, F. M., Somlo, G., Garberoglio, C., Paz, B., Shen, J., Lau, S. K., Quake, S. R., Brown, J. M., Weissman, I. L., Clarke, M. F. Long-term haematopoietic reconstitution by Trp53(-/-)p16(Ink4a-/-)p19(Arf-/-) multipotent progenitors. 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. Therapeutic Implications of the Cancer Stem Cell Hypothesis, Dysregulated gene expression networks in human acute myelogenous leukemia stem cells. Human T-cell leukaemia virus (HTLV), first isolated in the United States from a patient with cutaneous T-cell lymphoma, is a unique horizontally transmitted retrovirus which is highly associated with certain adult T-cell malignancies. In this report, we have used intravital multiphoton microscopy to visualize the different migration patterns of human breast tumor cells in live primary tumors. Finally, although the two human tumors were derived from diverse genetic backgrounds, we found that their migratory tumor cells exhibited coordinated gene expression changes that led to the same end-phenotype of enhanced migration involving activating actin polymerization and myosin contraction. Limited viral replication facilitates greater penetration of virions into tissue and can improve gene transfer. View details for DOI 10.1073/pnas.0610117104, View details for Web of Science ID 000243761100053. View details for Web of Science ID A1990DX36100002, View details for Web of Science ID A1989T821800013. We used xenograft tumors of MDA-MB-231 cells as well as a low passage xenograft tumor from orthotopically injected patient-derived breast tumor cells. Epithelial-to-mesenchymal transition has been shown to correlate with therapy resistance, but the functional link and signalling pathways remain to be elucidated. 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 cDNA library was constructed from the HUT102 cell line established from a patient with adult T-cell leukemia/lymphoma and screened for cDNA clones that contain (i) cellular sequences abundantly expressed in HUT102 cells and not in the virus-negative T-cell line HUT78, and (ii) viral long terminal repeat (LTR) sequences either in the 5' end or in the 3' end. Murine CD18 can be expressed on the cell surface of up to 20% of the mature cells generated by the culture system, suggesting that clinically significant levels of gene transfer may be occurring. CD137 activation, which was dependent on NK cell expression of the FcRIII receptor, occurred both in vitro and in the peripheral blood of women with HER2-expressing breast cancer after trastuzumab treatment. View details for Web of Science ID A1996WD32200005. This raises the issue of whether there is a conserved mechanism to effect self-renewing divisions. Clinically, successful reconstruction of human bone marrow would permit the controlled production of mature blood cells for transfusion therapy, and immature bone marrow stem cells for bone marrow transplantation. Unfortunately, although chemotherapy and/or radiation therapy can sometimes shrink tumors, metastatic cancers of epithelial origin are essentially incurable. These results suggest that Bcl-2 family members are required for survival of cancer cells derived from solid tissues. When purified from Matrigel contaminated LDV(+) tumors, sorted human breast tumor cells, as well as tumors grown from sorted cells, were shown to be LDV-free, as tested by PCR. View details for Web of Science ID A1995RY96700021. Additionally, it facilitated the identification of quiescent stem cells and revealed genes that contribute to breast tumorigenesis. BIO-IMEB - Biofilms in Industry, Medicine & Environmental Biot, Galway, Ireland, 9-14 August 2003. View details for DOI 10.1016/j.cell.2009.07.011, View details for Web of Science ID 000268771900022, View details for PubMedCentralID PMC2731699. 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. Filter By. Reya, T., Morrison, S. J., Clarke, M. F., Weissman, I. L. Clinical protocol. The human RGS18 ortholog has a tissue-specific expression pattern similar to that of mouse RGS18. Multiple cell lines expressing variable levels of exogenous temperature-sensitive p53 were generated. Furthermore, in several other nonhematopoietic tissues, cells could be separated into distinct subpopulations with differential Bmi-1 expression. 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