c-sis gene expression has been demonstrated in a variety of human tumors, although generally at levels much lower than those shown to transform cells in vitro. Thus, the development of proper sampling techniques or improved stem cell retention may be critical to obtain successful long-term cultures. Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. Parsels, L. A., Zellars, R. C., Loney, T. L., Parsels, J. D., Clarke, M. F., MERCHANT, A. K., Lawrence, T. S., Maybaum, J. Bcl-x(s) enhances adenoviral vector-induced apoptosis in neuroblastoma cells. 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. Synchronized cells allowed to pass out of G1 prior to being placed at 32.5 degrees C continued to cycle until subsequently arrested in G1; loss of viability occurred following G1 arrest. Parks, I. K., Klug, C. A., Li, K. J., Jerabek, L., Li, L. H., Nanamori, M., Neubig, R. R., Hood, L., Weissman, I. L., Clarke, M. F. A novel, conditionally replicative adenovirus for the treatment of breast cancer that allows controlled replication of E1a-deleted adenoviral vectors. 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. He is member of the Board of Parks Victoria. View details for Web of Science ID 000268227400008, View details for Web of Science ID 000209702603139, View details for Web of Science ID 000209701800291. Biotinylated granulocyte/macrophage colony-stimulating factor (GM-CSF) analogues with different linkage chemistries and levels of conjugated biotin were synthesized by reacting recombinant human GM-CSF with sulfosuccinimidyl 6-biotinamidohexanoate or biotin hydrazide/1-[3-(dimethylamino)-propyl]-3-ethylcarbodiimide. Al-Hajj, M., Becker, M. W., Wichal, M., Weissman, I., Clarke, M. F. Bmi1, stem cells, and senescence regulation. James Mallet (* 1955), Evolutionsbiologe und Entomologe. To determine the role of these proteins in maintaining cancer cell viability, an adenovirus vector that expresses bcl-xs, a functional inhibitor of these proteins, was constructed. However, the underlying molecular mechanisms are poorly characterized. Kim et al. He served as the Head of the School of Life Sciences from 2011-2019. Amy Smith Berylson Professor of Materials Science and Professor of Chemistry & Chemical Biology. Human tumors where evidence of cancer stem cells has been published include tumors of the breast, brain, pancreas, head and neck, and colon. Individual phenotypic cancer cell subsets were purified, and their tumor-initiating properties were investigated by injection in NOD/SCID mice. View details for Web of Science ID A1984SP90200011. The hair color is Light brown and the eye color is Blue. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. To study p53 trafficking, the jellyfish green fluorescent protein (GFP) was fused to the wild-type or mutated p53 proteins for fast and sensitive analysis of protein localization in human MCF-7 breast cancer, RKO colon cancer, and SAOS-2 sarcoma cells. 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. In contrast, no proviral methylation was detected in any of the cell lines examined, suggesting a functional correlation between methylation and viral RNA expression. Arthur C. Clarke, in full Sir Arthur Charles Clarke, (born December 16, 1917, Minehead, Somerset, Englanddied March 19, 2008, Colombo, Sri Lanka), English writer, notable for both his science fiction and his nonfiction. Receptor tyrosine kinase (RTK) inhibitors have advanced colon cancer treatment. Okamoto, T., Reitz, M. S., Clarke, M. F., JAGODZINSKI, L. J., WONGSTAAL, F. Sequence-specific interaction of histones with the simian virus 40 enhancer region in vitro. 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. Here we show that the gene encoding alpha-catenin (CTNNA1) is expressed at a much lower level in leukemia-initiating stem cells from individuals with AML or MDS with a 5q deletion than in individuals with MDS or AML lacking a 5q deletion or in normal hematopoietic stem cells. Patsialou, A., Bravo-Cordero, J., Wang, Y., Liu, H., Clarke, M. F., Condeells, J. S. Deregulation of stem cell self-renewal pathways in cancer, MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11. He wanted to play football in high school, but his mother wouldn't let him, afraid that he would get hurt. View details for Web of Science ID A1992JB22100010. Michael Clark. Their scholarship is deepening our understanding of learning while changing policy and practice. In addition to his clinical duties in the division of Oncology, Dr . Our results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs. When combined with the prognostic criteria of the National Institutes of Health, the IGS was used to stratify patients with high-risk early breast cancer into prognostic categories (good or poor); among patients with a good prognosis, the 10-year rate of metastasis-free survival was 81%, and among those with a poor prognosis, it was 57%. Also, HTLV can be transmitted in vitro to cord blood T-lymphocytes. These studies show that the human retrovirus HTLV, which has been demonstrated to be associated with certain T cell malignancies, can infect B cells or B cell precursors. BIO-IMEB - Biofilms in Industry, Medicine & Environmental Biot, Galway, Ireland, 9-14 August 2003. Michael Clarke Duncan was born on December 10, 1957 in Chicago, Illinois. Chemotherapy resistance frequently drives tumour progression. These data suggest that the c-myb protooncogene encodes alternately spliced mRNA species with opposing effects on differentiation. He is so driven about his work and is so charismatic to his students. View details for Web of Science ID A1994PC47400008. In addition to clinical duties in oncology, Dr. Clarke maintains a laboratory . We found that each antibody inhibited tumor growth and that the combination of the two antibodies was more effective than either alone. 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. KIT signaling promotes growth of colon cancer cells and organoids in culture and xenograft tumors in mice via its ligand, KITLG, in an autocrine or paracrine manner. 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. Michael Clarke was the original drummer of the Byrds, appearing on their first five albums before leaving around the end of 1967.Clarke was the least talented of the five members that were on the Byrds' 1965-1967 recordings, as unlike the others as could be, since he did almost no songwriting. We hypothesized that if non-tumorigenic cells are more susceptible to chemotherapeutic agents, then residual tumors might be expected to contain a higher frequency of CoCSC.Xenogeneic tumors initiated with CoCSC were allowed to reach approximately 400 mm(3), at which point mice were randomized and chemotherapeutic regimens involving cyclophosphamide or Irinotecan were initiated. The main battle tanks have a maximum speed of around 43.5mph and a range of . As few as 100 cells with this phenotype were able to form tumors in mice, whereas tens of thousands of cells with alternate phenotypes failed to form tumors. In this issue of Cell Stem Cell, Hermann et al. High-level expression of the c-sis oncogene, which encodes the beta chain of platelet-derived growth factor, transforms immortalized rodent fibroblasts in vitro to a malignant phenotype. The Shep-1 neuroblastoma cell line is highly resistant to IR. LDV infects specifically mouse macrophages and alters immune system and tumor phenotype. Effective treatment of cancer will require therapeutic strategies that are able to target and eliminate this tumorigenic subset of cells. Our studies show that coincident expression of human Bcl-2 protein with p53 prolongs survival of murine erythroleukemia cells. The ability to self-renew is essential for all kinds of stem cells regardless of tissue type. View details for Web of Science ID A1992HP64200009. At a meeting of the Translation Research Program of the Radiation Therapy Oncology Group held in early 2008, attendees focused on updating the current state of knowledge in cancer stem cell research and discussing ways in which this knowledge can be translated into clinical use across all disease sites. A shift-up in medium perfusion rates from 3.5/week to 7/week resulted in increased metabolic rates that resembled those observed in the cultures that were exchanged at the 7/week rate throughout, showing that the metabolic rates could be directly controlled by the perfusion rate. We have previously shown that two human T-cell lines (HSB and 8402) derived from patients with childhood T-cell ALL (T-ALL) do not synthesize detectable mRNA for HLA-DR alpha. Programmed cell death, or apoptosis, may play an important role in the regulation of hematopoiesis. Dr Michael Clarke is Associate Professor at the National Security College, Crawford School of Public Policy, Australian National University, and Director of the ANU-Indiana University Pan-Asia Institute. Our study identifies both epithelial-mesenchymal transition (EMT) and active MAPK/ERK signaling in tumors that adapt to oncogenic KrasG12D withdrawal in a novel Trp53-/- breast cancer mouse model. Best response after ABMT included: two CR, one CR surgically NED, five PR, three PR surgically NED, seven SD, and eight PD. Emerging evidence has suggested that the capability of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. Three well-known tumor suppressors, p53, p16INK4a, and p19ARF, have been connected to the limiting of stem cell self-renewal and proliferation. View details for Web of Science ID 000171898900054. Furthermore, the tumorigenic CD44(+) cells differentially express the BMI1 gene, at both the RNA and protein levels. 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. The successful ex vivo reconstruction of human bone marrow is an extraordinarily important basic scientific and clinical goal. Single-cell RNA sequencing confirms the accumulation of T cells and B cells in adipose tissue-including plasma cells that express immunoglobulin J-which also accrue concurrently across diverse organs. No activating mutations in KIT were detected in DLD1, POP77, or UM-COLON#8 cells. Interest in single-cell whole-transcriptome analysis is growing rapidly, especially for profiling rare or heterogeneous populations of cells. Liu, H., Patel, M., Prescher, J., Qian, D., Dalerba, P., Lin, J., Shimono, Y., Dirbas, F., Contag, C., Gambhir, S., Clarke, M. What can we learn about self renewal and drug resistance from the isolation of epithelial tumor stem cells? ALTERATION OF P53 CONFORMATION AND INDUCTION OF APOPTOSIS IN A MURINE ERYTHROLEUKEMIA CELL-LINE BY DIMETHYLSULFOXIDE, C-MYC AND BCL-2 MODULATE P53 FUNCTION BY ALTERING P53 SUBCELLULAR TRAFFICKING DURING THE CELL-CYCLE. Han, J. S., Qian, D. L., Wicha, M. S., Clarke, M. F. Targeting cancer cell death with a bcl-x(s) adenovirus. This has been recently shown in an in vivo model, where overexpression of Bcl-XL, is a crucial step in the progression from hyperplasia to neoplasia and is accompanied by a significant decrease in tumor apoptosis [56]. Park, I. K., Qian, D. L., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., Morrison, S. J., Clarke, M. F. Prospective identification of tumorigenic breast cancer cells. Liu, H., Bockhorn, J., Dalton, R., Olopade, O. F., Clarke, M. F., Greene, G. L. MicroRNAs regulating breast cancer stem cells and metastasis. Three seminoma patients remain progression-free. 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. Cai, S., Kalisky, T., Sahoo, D., Dalerba, P., Feng, W., Lin, Y., Qian, D., Kong, A., Yu, J., Wang, F., Chen, E. Y., Scheeren, F. A., Kuo, A. H., Sikandar, S. S., Hisamori, S., van Weele, L. J., Heiser, D., Sim, S., Lam, J., Quake, S., Clarke, M. F. Targeted chromatin ligation, a robust epigenetic profiling technique for small cell numbers. 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. BACKGROUND: Recent studies in murine mammary tissue have identified functionally distinct cell populations that may be isolated by surface phenotype or lineage tracing. View details for DOI 10.1371/journal.pone.0002428, View details for Web of Science ID 000263280700013, View details for PubMedCentralID PMC2413402, View details for Web of Science ID 000454834700190. View details for DOI 10.1634/stemcells.2007-0440, View details for Web of Science ID 000253372600008. . Usp16 contributes to somatic stem-cell defects in Down's syndrome. A temperature-sensitive mutant of murine p53 (p53Val-135) was transfected by electroporation into murine erythroleukemia cells (DP16-1) lacking endogenous expression of p53. View details for Web of Science ID 000178077600006. Imatinib inhibited growth of KIT(+) colon cancer organoids in culture and growth of xenograft tumors in mice. PROF. MICHAEL CLARKE (Director, Royal United Services Institute): I think the United States has been behind us in this respect. To test this hypothesis, murine erythroleukemia cells were transfected with bcl-XL and p53ts. From August 1990 to June 1998, 29 males (25 NSGCT) were treated. View details for Web of Science ID 000076744000010. We have studied the ability of c-myc and bcl-2 oncogenes to modulate p53 function. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. Liu, R., Wang, X., Chen, G. Y., Dalerba, P., Gurney, A., Hoey, T., Sherlock, G., Lewicki, J., Shedden, K., Clarke, M. F. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. When a virus expressing the proapoptotic gene Bc1-xs (Clarke et al., Proc. We demonstrate that reversing impaired NPC self-renewal via genetic reduction of USP16, a histone modifier and critical physiological antagonist of the Polycomb Repressor Complex 1, can prevent downstream cognitive defects and decrease astrogliosis in vivo. Zanini, F. n., Berghuis, B. Replication-deficient viral vectors are currently being used in gene transfer strategies to treat cancer cells. 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. Here we implement single-cell PCR gene-expression analysis to dissect the cellular composition of primary human normal colon and colon cancer epithelia. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. 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. We developed a new technique that replaces immunoprecipitation with a simplified chromatin fragmentation and proximity ligation step that eliminates bead purification and washing steps. Hoey, T., Yen, W., Axelrod, F., Basi, J., Donigian, L., Dylla, S., Fitch-Bruhns, M., Lazetic, S., Park, I., Sato, A., Satyal, S., Wang, X., Clarke, M. F., Lewicki, J., Gurney, A. Bmi-1-green fluorescent protein (GFP)-knock-in mice reveal the dynamic regulation of Bmi-1 expression in normal and leukemic hematopoietic cells. However, at later times X-ray irradiated parental DP16-1 cells also had decreased survival compared to the unirradiated control. The combination of tissue-specific and tumor-specific elements offers the possibility to artificially develop such promoters. Park, I., Qian, D., Kiel, M., Becker, M., Prohaska, S., Weissman, I., Morrison, S., Clarke, M. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. All three analogues retained full agonist activity relative to the native protein (EC50 = 10-15 pM) when assayed for the stimulation of human bone marrow progenitor cell growth. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). We show that a set of active constituent enhancers, located within the two CD47 SEs, regulate CD47 expression in different cancer cell types and that disruption of CD47 SEs reduces CD47 gene expression. This report summarizes the major topics discussed and the future directions that research should take. Flow cytometry and microfluidics-based single-cell multiplex RT-PCR allowed dissection of IFN responses in single RV-infected and bystander intestinal epithelial cells (IECs). Anaesthesia 2001, 56(5), 486-487. The C57BL/Ka-Thy-1.1 alleles were partially dominant. The miR-30c-VIM/TWF1 signaling cascade is also associated with clinical outcome in breast cancer patients. View details for DOI 10.1016/j.ijrobp.2009.03.047, View details for Web of Science ID 000268346100041. He is a board certified oncologist with extensive training in molecular biology and stem cell biology. Stromal Gli2 activity coordinates a niche signaling program for mammary epithelial stem cells. Because these observations conflict with previously suggested models for FdUrd-induced damage to parental DNA, we propose an alternative model to explain how incorporation of uracil into nascent DNA might result in single-strand breaks in the opposite (parental) strand and how these breaks might be converted to the double-strand breaks that produce cell death. Chromatin immunoprecipitation (ChIP) is a powerful assay used to probe DNA-protein interactions. Cell migration is an essential component of almost every step of the metastatic cascade, especially the early step of invasion inside the primary tumor. Bockhorn, J., Dalton, R., Nwachukwu, C., Huang, S., Prat, A., Yee, K., Chang, Y., Huo, D., Wen, Y., Swanson, K. E., Qiu, T., Lu, J., Park, S. Y., Dolan, M. E., Perou, C. M., Olopade, O. I., Clarke, M. F., Greene, G. L., Liu, H. MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion. Usp16 copy number normalization restores normal Wnt activation in Ts65Dn mice models. The results demonstrate that cell sorting is effective, much faster and less likely to alter tumor cell phenotype than traditional methods for removing LDV from xenograft models. View details for DOI 10.1056/NEJMc1602584, View details for PubMedCentralID PMC4955394. 29 Oxford St, Pierce 229. jaiz@seas.harvard.edu (617) 495-3558. A., Chen, L., Levy, R. Removal of lactate dehydrogenase-elevating virus from human-in-mouse breast tumor xenografts by cell-sorting. Here we describe two such clones and report that one of them transforms NIH-3T3 cells. 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. View details for Web of Science ID A1991FC72500007. We assessed tumorigenicity using limiting dilution analysis.KIT and KITLG were expressed heterogeneously by a subset of human colon tumors. New treatment modalities are needed for the latter group. Professor Michael Clarke, Director of the Royal United Services Institute and a graduate of the Department of International Politics, was honoured as Fellow of Aberystwyth University on Tuesday 10 July. MicroRNAs (miRNAs) are important regulators of stem and progenitor cell functions. View details for DOI 10.1038/s41586-022-04461-2. [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. Michael Clarke is a UK academic and "terror expert". Isobe, T., Zarnegar, M. A., Abdel-Wahab, O., Clarke, M. F. A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer. This is accompanied by a translocation of the p53 protein from the cytoplasm to the nucleus. Amine-derivatized analogues of 1.2 and 3.8 mol of biotin/mol of protein (N1-bGM-CSF and N4-bGM-CSF) and a carboxyl-modified analogue of 4.6 mol of biotin/mol of protein (C5-bGM-CSF) were synthesized. CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. 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. Adjunct Professor Michael Whitehouse. Two populations of cells, HSCs and MPP cells, were compared for differential gene expression using microarray analysis. CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer. Science-Fiction, auch Sciencefiction geschrieben ([sans fkn]; englisch science: Naturwissenschaft, fiction: Fiktion), ist ein Genre in Literatur (Prosa, Comic), Film, Hrspiel, Videospiel und Kunst.Charakteristisch sind wissenschaftlich-technische Spekulationen, Raumfahrtthemen, ferne Zukunft, fremde Zivilisationen und meist zuknftige Entwicklungen. Professor Clarke is a former Deputy Vice . Its expansion is a tightly regulated process, fueled by the mammary stem cells and these cells' unique property of self-renewal. We find that normal, regenerating, and developing gland maintain a specific branching pattern. Ayash, L. J., Clarke, M., Silver, S. M., Braun, T., Uberti, J., Ratanatharathorn, V., Reynolds, C., Ferrara, J., Broun, E. R., Adams, P. T. Evaluation of a new dual-specificity promoter for selective induction of apoptosis in breast cancer cells. View details for DOI 10.1016/j.stemcr.2020.12.012. 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