From 1990 to 2001 he was the founding Director of the Centre for Defence Studies at King's. Ryan, J. J., Prochownik, E., Gottlieb, C. A., Apel, I. J., Merino, R., Nunez, G., Clarke, M. F. CELL-CYCLE ANALYSIS OF P53-INDUCED CELL-DEATH IN MURINE ERYTHROLEUKEMIA-CELLS. The tight regulation of E1A expression correlated with the ability of these viruses to replicate and kill human cancer cells that express estrogen receptors, or are maintained under hypoxic conditions. Mcl1, Tel/Etv6, Gfi1, Pten and Stat5) have been identified. A gene expression analysis revealed that the expression of stem cell associated genes, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice. Our objective was to identify a mouse model of breast cancer stem cells that could have relevance to the study of human breast cancer. 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). 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. 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. 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. The IGS was also associated with the prognosis in medulloblastoma (P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01). Our laboratory has developed a novel mouse model that reliably permits individual cancer cells isolated directly from patients' tumors to be assayed. Furthermore, we found that specifically inhibiting human DLL4 in the tumor, either alone or in combination with the chemotherapeutic agent irinotecan, reduced cancer stem cell frequency, as shown by flow cytometric and in vivo tumorigenicity studies. In experiments on nude mice bearing HeLa ascites tumors, intraperitoneal injection of AdRSVlaclys/pE1 resulted in a significantly higher percentage of infected HeLa cells as compared with the PBS controls (p < 0.05) or the AdRSVlaclys/pUC19 controls (p < 0.01). In spite of substantial differences in the extent of methylation of class I-related genes, no obvious differences exist among these cell types in their levels of expression of HLA-A and -B antigens. The CSD could block the binding of p53 to the NLS receptor, importin alpha, and reduce the efficiency of p53 nuclear import in MCF-7, H1299, and Saos-2 cells. To evaluate the feasibility of positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) in patients with germ cell tumor (GCT) to monitor treatment and differentiate residual masses after chemotherapy.Twenty-six FDG PET studies were performed in 21 patients with GCT, FDG uptake of tumors was interpreted visually, and the lean standardized uptake value (SUVlean) was determined. View details for DOI 10.1016/j.semradonc.2008.11.002, View details for Web of Science ID 000264310800003, View details for PubMedCentralID PMC2789266. Adjunct Associate Professor David Welsh. Although an increasing number of interventions show promise for rejuvenation2, their effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. View details for Web of Science ID A1990DX36100002, View details for Web of Science ID A1989T821800013. This demands a complex crosstalk between extrinsic signals from the microenvironment and the cell-intrinsic regulators of self-renewal. Kohrt, H. E., Houot, R., Weiskopf, K., Goldstein, M., Lund, P., Scheeren, F., Czerwinski, D., Colevas, A. D., Weng, W., Clarke, M. F., Carlson, R. W., Sunwoo, J., Tedder, T., Chen, L., Levy, R. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. 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. While cell lines expressing p53 alone rapidly died, those cells co-expressing Bcl-XL survived. Taken together, these results indicate that wild-type p53 induces cell death in murine erythroleukemia cells and that this effect occurs predominantly in the G1 phase of actively cycling cells. Knockdown of endogenous miR-142 effectively suppressed organoid formation by BCSCs and slowed tumor growth initiated by human BCSCs in vivo. View details for DOI 10.1016/j.stem.2016.11.007, View details for PubMedCentralID PMC5341693. This transcriptomic atlas-which we denote Tabula Muris Senis, or 'Mouse Ageing Cell Atlas'-provides molecular information about how the most important hallmarks of ageing are reflected in a broad range of tissues and cell types. The stem cells maintain themselves through a process known as self-renewal. Although cancer cell lines provide invaluable information, their biological properties often differ in crucial ways from de novo cancer cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. In mammary glands, reduced levels of Usp16 increase tissue responsiveness to Wnt, resulting in upregulation of the downstream Wnt target Axin2, expansion of the basal compartment and increased in vitro and in vivo epithelial regeneration. This makes it virtually impossible to infect the majority of tumor cells in vivo and results in inadequate gene transfer. Professor Michael Clarke was Director-General of the Royal United Services Institute (RUSI) from 2007 to 2015 when he retired from that role. View details for Web of Science ID A1991FC72500007. 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. Dr Michael Clarke is an internationally recognised expert on the history and politics of the Xinjiang Uyghur Autonomous Region, People's Republic of China (PRC), Chinese foreign policy in Central Asia, Central Asian geopolitics, nuclear proliferation and non-proliferation and American grand strategy and foreign policy. Mark Malloch Brown, Baron Malloch-Brown (* 1953), Politiker und stellvertretender Generalsekretr der Vereinten Nationen. View details for DOI 10.1053/j.gastro.2012.02.006, View details for Web of Science ID 000303113600038, View details for PubMedCentralID PMC3911891. Clarke, M. F., Westin, E., Schmidt, D., Josephs, S. F., Ratner, L., WONGSTAAL, F., Gallo, R. C., Reitz, M. S. IDENTIFICATION OF THE HUMAN T-CELL LYMPHOMA VIRUS IN B-CELL LINES ESTABLISHED FROM PATIENTS WITH ADULT T-CELL LEUKEMIA. Liu, H., Bockhorn, J., Dalton, R., Olopade, O. F., Clarke, M. F., Greene, G. L. MicroRNAs regulating breast cancer stem cells and metastasis. View details for Web of Science ID 000186230600042, View details for PubMedCentralID PMC2614897, View details for Web of Science ID 000184162600127. Within 24-48 hr, viral RNA expression increased at least four- to eightfold. We show that a minority population of CD44(+) cancer cells, which typically comprise <10% of the cells in a HNSCC tumor, but not the CD44(-) cancer cells, gave rise to new tumors in vivo. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. A panel of NB cell lines (CHP-382, GOTO, SHEP-1, SHSY-5Y, and GI-CA-N) were infected with either a bcl-xS adenovirus (pAdRSV-bcl-xS) or a control virus (pAdRSV-lac-z). Genetic upregulation of the Wnt pathway in Ts65Dn mice rescues the proliferation defect observed in mammary epithelial cells. Professor Clarke's current research interests are the molecular mechanisms of cell division, chromosome instability and mitotic cell death. This is the first example of transformation of NIH-3T3 cells by a human onc gene other than c-ras or Blym, as well as the first demonstration of transformation by a human cDNA clone. His passion is to see government conservation policy based on the best available. Recently, his group described a molecular mechanism that confers resistance to radiation in breast cancer stem cells. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. View details for DOI 10.1016/j.gde.2006.08.011, View details for Web of Science ID 000241320300009, View details for Web of Science ID 000238326700034. No activating mutations in KIT were detected in DLD1, POP77, or UM-COLON#8 cells. The fragment with a tandem repeat of the 72-bp element also does not associate randomly with histones. The molecular mechanisms that control the self-renewal of HSCs are still largely unknown. 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. He was Director General of the Royal United Services Institute from 2017-2015 and is now a Distinguished Fellow at RUSI. 2010). View details for Web of Science ID 000345777300014. T47D cells were then transfected with a temperature-sensitive mutant of the tumor suppressor p53 (p53ts). A central issue in stem cell biology is to understand the mechanisms that regulate the self-renewal of haematopoietic stem cells (HSCs), which are required for haematopoiesis to persist for the lifetime of the animal. After 5-azacytidine treatment of the cell lines, all cells expressed Ig light chains. Ealovega, M. W., McGinnis, P. K., Sumantran, V. N., Clarke, M. F., Wicha, M. S. A RECOMBINANT BCL-X(S) ADENOVIRUS SELECTIVELY INDUCES APOPTOSIS IN CANCER-CELLS BUT NOT IN NORMAL BONE-MARROW 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. Adorno, M., di Robilant, B. N., Sikandar, S. S., Acosta, V. H., Antony, J., Heller, C. H., Clarke, M. F. Usp16 modulates Wnt signaling in primary tissues through Cdkn2a regulation. Cells that were kept density arrested at 32.5 degrees C (G0) lost viability at a much slower rate than did cells released into G1. 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. Expression of p16Ink4a and p19Arf in normal HSCs resulted in proliferative arrest and p53-dependent cell death, respectively. 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. Professor Michael Clarke, former director of the defence think tank Rusi said: "Often these symbols will be location-based - they will be communicating where a unit is heading. View details for Web of Science ID A1991EY27300001. To solve this problem, a new generation of tumor-specific, conditionally replicative adenoviruses is being developed. By complementation of the E1a protein in trans, Ad5ERE2 allows restricted replication of a conventional E1a-deleted adenoviral vector. Metastasis remains a significant challenge in treating cancer. Patients with KIT-expressing colon tumors can benefit from KIT RTK inhibitors. It has been viewed by tens of millions of people around the world, including in China, where Sandel was named the "most . However, none of the NB cell lines expressed Bcl-xS. Furthermore, we identify unique, CSC-specific, remodeling events. Here we developed a CSC model for the study of human colorectal cancer (CRC). 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. To test this hypothesis, murine erythroleukemia cells were transfected with bcl-XL and p53ts. Current page 1; Page 2; Haematopoiesis is maintained by a hierarchical system where haematopoietic stem cells (HSCs) give rise to multipotent progenitors, which in turn differentiate into all types of mature blood cells. Zabala, M., Lobo, N. A., Seoane, J. Inhibiting USP16 rescues stem cell aging and memory in an Alzheimer's model. 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. 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. This includes loss of a portion of the region involved in transcription activation as well as a separate highly conserved domain. View details for Web of Science ID 000083623000026. In the present study, further mutagenesis analyses were carried out between Lys-305 and the major nuclear localization signal (NLS I) of p53. James Mallet (* 1955), Evolutionsbiologe und Entomologe. 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. View details for DOI 10.1016/j.jcmgh.2017.01.006. Since stromal cells in traditional human bone marrow cultures produce little HGFs, we have begun by asking whether local supplementation of hematopoietic growth factors via genetically engineered stromal cells might augment hematopoiesis in liquid cultures. 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. Ailles, L., Prince, M., Joshua, B., Doweck, I., Kaplan, M., Clarke, M., Weissman, I. George Malcolm (1917-1997), Pianist, Cembalist, Dirigent und Komponist. Following high-dose IR, cell fractionation demonstrated that p53 is induced and targeted to the nucleus. Effective treatment of cancer will require therapeutic strategies that are able to target and eliminate this tumorigenic subset of cells. 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. Its expansion is a tightly regulated process, fueled by the mammary stem cells and these cells' unique property of self-renewal. He is a board certified oncologist with extensive training in molecular biology and stem cell biology. The Thy-1+CD24medCD49fhigh phenotype contained the majority of the serially transplantable epithelial cells. This suggests that agents that target the defective self-renewal pathways in cancer cells might lead to improved outcomes in the treatment of these diseases. View details for Web of Science ID A1984SP90200011. Here, we report the results of using a bioreactor system to expand hematopoietic cells after a brief retrovirus infection using a high titer, replication defective virus encoding for murine CD18. These findings have implications for the development of effective therapeutic agents targeting tumor-initiating cells. View details for DOI 10.1016/j.stem.2020.06.017, View details for DOI 10.1056/NEJMra1804280, View details for DOI 10.1056/NEJMc1908886, View details for Web of Science ID 000440602000017. Loss of Bcl11b leads to a Cdkn2a-dependent exhaustion of ductal epithelium and loss of epithelial cell regenerative capacity. Using single-cell transcriptomic data, we assessed cell-type-specific manifestations of different hallmarks of ageing-such as senescence3, genomic instability4 and changes in the immune system2. To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. The C57BL/Ka-Thy-1.1 alleles were partially dominant. They discuss the increasing threat of China, the post-Brexit identity of "Global Britain" and how the . Comparing the expression signature of normal HSC to that of LSC, we identified 3,005 differentially expressed genes. This promoter induces transcriptional activation of the E1a and E4 units in response to estrogens in cells that express the ERs. Emerson, S. G., Palsson, B. O., Clarke, M. F., Silver, S. M., Adams, P. T., Koller, M. R., Van Zant, G., Rummel, S., Armstrong, R. D., MALUTA, J. His group was the first to discover that the proto-oncogene Bmi-1 regulates stem cell self-renewal via an epigenetic mechanism. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Professor Clark is someone that should teach all students. He has published internationally on the ecology and conservation biology of birds, reptiles, mammals, fish and plants. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Reinitz, F., Chen, E. Y., Nicolis di Robilant, B., Chuluun, B., Antony, J., Jones, R. C., Gubbi, N., Lee, K., Ho, W. H., Kolluru, S. S., Qian, D., Adorno, M., Piltti, K., Anderson, A., Monje, M., Heller, H. C., Quake, S. R., Clarke, M. F. LEFTY1 Is a Dual-SMAD Inhibitor that Promotes Mammary Progenitor Growth and Tumorigenesis. 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. Fifteen (52%) received both transplants. G418-resistant clones, which expressed the c-sis cDNA, were selected and characterized. Resolution of "averaged" innate immune responses in single IECs thus revealed unexpected heterogeneity in both the induction and subversion of early host antiviral immunity, which modulated host range. 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. 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). Here we performed single-cell RNA sequencing on 20 organs to reveal cell-type-specific responses to young and aged blood in heterochronic parabiosis. Using terminal transferase-mediated dUTP-digoxigenin nick end labeling, we observed apoptotic cells at sites of bcl-xs adenoviral injection. 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 HUT-102 cell line, derived from a cutaneous T-cell lymphoma and infected with HTLV, expresses several cellular oncogenes. Three seminoma patients remain progression-free. 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. We collected eleven pancreatic tumors and identified three shared and five private neoplastic cell populations, offering insight into the origins of neuroendocrine and exocrine tumors. Street. These include the nuclear import and export signals of p53, inhibition of p53 nuclear import and export by oligomerization, MDM2-mediated p53 nuclear export, and possible roles of p53 phosphorylation in regulating p53 cellular localization. Sky's defence analyst Prof Michael Clarke gives his opinion on the critical elements of the war in Ukraine and on what could come next Why you can trust Sky News Watch Next Tuesday's Press Preview PM announces 'major breakthrough' Baroness Betty Boothroyd dies A day of history, a day of reckoning On the frontline in Vuhledar We found that adult and fetal mouse and adult human HSCs express the proto-oncogene Bmi-1. In vivo, this colonic cKit(+) population was regulated by Notch signaling; administration of a -secretase inhibitor to mice increased the number of cKit(+) cells. Rachel Ellehuus. Treatment-related mortality was 10%. In order to better understand HSC self-renewal, we need to understand how these pathways are coordinated. Here we describe two such clones and report that one of them transforms NIH-3T3 cells. In Down's Syndrome (DS), triplication of Usp16 dampens the activation of the Wnt pathway. Interest in single-cell whole-transcriptome analysis is growing rapidly, especially for profiling rare or heterogeneous populations of cells. Finally we report that the TNF-NFKB1 signalling pathway directly regulates CD47 by interacting with a constituent enhancer located within a CD47-associated SE specific to breast cancer. War in Ukraine 2022: Prof. Michael Clarke analysis 116 videos 3,380 views Updated 5 days ago Defence and security analyst Professor Michael Clarke's observations mostly on Sky News. Regulation of the Wnt pathway in stem cells and primary tissues is still poorly understood. These experiments demonstrate the feasibility of using bcl-xs gene therapy to induce apoptosis in human breast tumors. One of the best candidate genes involved in conferring self-renewal capacity is Bmi-1, which has been proven to be essential for the maintenance of both normal adult hematopoietic and leukemia stem cells, as well as adult neural stem cells. Published algorithms for automatic cell annotation are limited to known cell types and fail to capture novel populations, especially cancer 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. Thus a limiting serum component is responsible for the altered metabolic and growth rates. 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. RRV replication was significantly rescued in IFN types I and II, as well as STAT1 (IFN types I, II, and III) deficient mice in contrast to EW, which was only modestly sensitive to IFNs I and II. 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. These results suggest that the activity of some mutant p53 proteins can be functionally modified by exogenous compounds. These included transcription factors, signaling molecules, and previously unknown genes. 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? Traditional methods of implementing this assay are lengthy, cumbersome and require a large number of cells, making it difficult to study rare cell types such as certain cancer and stem cells. This observation is traditionally explained by postulating variations in tumor microenvironment and coexistence of multiple genetic subclones, created by progressive and divergent accumulation of independent somatic mutations. - Associate Professor: Business Management Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. These studies show that the metabolic and secretory behavior of genetically engineered cells is influenced by the medium exchange schedule. Profiles. The successful ex vivo reconstruction of human bone marrow is an extraordinarily important basic scientific and clinical goal. Professor Clarke was presented by Professor Len Scott from the Department of International Politics. Morrison, S. J., Qian, D., Jerabek, L., Thiel, B. However, KITLG-knockdown DLD1 cells formed smaller xenograft tumors than control cells. Transient overexpression of RGS18 attenuated inositol phosphates production via angiotensin receptor and transcriptional activation through cAMP-responsive element via M1 muscarinic receptor. We were able to distinguish the tumorigenic (tumor initiating) from the nontumorigenic cancer cells based on cell surface marker expression. These chemically reactive forms of biotin produced derivatives biotinylated at amine or carboxyl groups, respectively. Other pathways have not been previously implicated in the regulation of cancer stem cell functions, including Ribosome and T Cell Receptor Signaling pathway. View details for Web of Science ID 000255592400041, View details for Web of Science ID 000246136200023. 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%. 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. Hernandez-Alcoceba, R., Pihalja, M., Qian, D. L., Clarke, M. F. Differential gene expression profiling of adult murine hematopoietic stem cells. Rapid medium exchanged LTHBMCs were established on surfaces precoated with human natural fibronectin and type 1 rat tail collagen. Sumantran, V. N., Ealovega, M. W., Nunez, G., Clarke, M. F., Wicha, M. S. In vitro expansion of hematopoietic cells for clinical application. Conversely, genetic augmentation of Hedgehog response and systemic small-molecule Hedgehog pathway activation potently ameliorate colitis and restrain initiation and progression of colitis-induced adenocarcinoma. This new model for cancer will have significant ramifications for the way we study and treat cancer. View details for DOI 10.1038/sj.onc.1207947, View details for Web of Science ID 000223998800013, View details for Web of Science ID 000223225500005. We identify two distinct super-enhancers (SEs) associated with CD47 in certain cancer cell types. Recently, various new players that regulate HSC maintenance (e.g. Only a small minority of cancer cells had the capacity to form new tumors in a xenograft model. 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". 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