Bmi1 is required for the maintenance of adult stem cells in some tissues partly because it represses genes that induce cellular senescence and cell death. The cumulative data provide the foundation for an atlas of transcriptomic cell biology. 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. Using terminal transferase-mediated dUTP-digoxigenin nick end labeling, we observed apoptotic cells at sites of bcl-xs adenoviral injection. Clarke M, Mitchell KW, Goodship J, McDonnell S, Barker MD, Griffiths ID, McKie N. Clinical features of a novel TIMP-3 mutation causing Sorsby's fundus dystrophy: implications for disease mechanism. 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. Knockdown of endogenous miR-142 effectively suppressed organoid formation by BCSCs and slowed tumor growth initiated by human BCSCs in vivo. Xenograft tumors were grown from control and KIT-knockdown DLD1 and UM-COLON#8 cells in immunocompromised mice and compared. An alternately spliced c-myb mRNA encodes a truncated version of p75c-myb (mbm2) that includes the DNA binding region and nuclear localization signal present in the c-myb protein, but does not contain the transcriptional regulatory regions. Furthermore, the LTBMCs produced nonadherent colony-forming unit-GM (CFU-GM) for more than 20 weeks. View details for Web of Science ID 000083623000026. BIO-IMEB - Biofilms in Industry, Medicine & Environmental Biot, Galway, Ireland, 9-14 August 2003. Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy. We examined such heterogeneity in the small intestine during rotavirus (RV) infection. Prince, M. E., Sivanandan, R., Kaczorowski, A., Wolf, G. T., Kaplan, M. J., Dalerba, P., Weissman, I. L., Clarke, M. F., Ailles, L. E. Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. 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. Genetic upregulation of the Wnt pathway in Ts65Dn mice rescues the proliferation defect observed in mammary epithelial cells. Transplanted fetal liver and bone marrow cells obtained from Bmi-1-/- mice were able to contribute only transiently to haematopoiesis. To date, therapies targeting end-stage disease plaques, tangles, or inflammation have limited efficacy. In many cases, one of these abnormalities is an inhibition of PCD, which provides a selective advantage for tumor cells. van Weele, L. J., Djomehri, S. I., Cai, S., Antony, J., Sikandar, S. S., Qian, D., Ho, W. H., West, R., Scheeren, F. A., Clarke, M. F. Publisher Correction: Cell types of origin of the cell-free transcriptome. Thus, the ECMs used did not significantly influence the cell productivity of LTHBMCs. The IGS was also associated with the prognosis in medulloblastoma (P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01). View details for DOI 10.1016/j.stem.2013.06.012. Cancer stem cells and tumor metastasis: First steps into uncharted territory, Bmi-1-green fluorescent protein-knock-in mice reveal the dynamic regulation of Bmi-1 expression in normal and leukemic hematopoietic cells. FUKUNAGAJOHNSON, N., Ryan, J. J., Wicha, M., Nunez, G., Clarke, M. F. OVEREXPRESSION OF BCL-X(S), SENSITIZES MCF-7 CELLS TO CHEMOTHERAPY-INDUCED APOPTOSIS. Here we investigate the roles of these three proteins in the regulation of self-renewal and proliferation of mammary epithelial cells. The hair color is Light brown and the eye color is Blue. Here we developed a CSC model for the study of human colorectal cancer (CRC). Other pathways have not been previously implicated in the regulation of cancer stem cell functions, including Ribosome and T Cell Receptor Signaling pathway. 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). Additionally, it facilitated the identification of quiescent stem cells and revealed genes that contribute to breast tumorigenesis. Although these culture conditions still fall short of full reconstitution of functional human bone marrow, they provide an improved approach to hematopoietic cell culture that may permit the expansion and manipulation of progenitor cells in vitro. Mutagenesis analysis demonstrated that a single amino acid mutation of Lys-305 (mt p53) caused cytoplasmic sequestration of the p53 protein in the MCF-7 and RKO cells, whereas the fusion protein was distributed in both the cytoplasm and the nucleus of SAOS-2 cells. In several forms of human cancer, only a phenotypic subset of cancer cells, usually termed "cancer stem cells" (CSC), can initiate tumor growth when transplanted. 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. Although wild-type p53 is expressed in virtually all neuroblastoma tumors, treatment failures secondary to inadequate local control with radiotherapy are a problem in patients with advanced stage disease. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. A better understanding of the molecular mechanisms underlying metastasis is needed to develop more effective treatments. We thus identify stromal cells as cellular coordinators of colon inflammation and suggest their pharmacologic manipulation as a potential means to treat colitis. In approaching the bone marrow culture system, we recognize the critical role that hematopoietic growth factors (HGFs) play in hematopoiesis. View details for DOI 10.1016/j.cell.2009.07.011, View details for Web of Science ID 000268771900022, View details for PubMedCentralID PMC2731699. 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. After 5-azacytidine treatment of the cell lines, all cells expressed Ig light chains. These data indicate that the simultaneous regulation of E1A and E4 viral transcription units by the appropriate combination of promoters can increase the tumor selectivity of oncolytic adenoviruses. Replication-defective retroviruses are frequently used as gene carriers for gene transfer into target cells. Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. Stem cells in many tissues sustain themselves by entering a quiescent state to avoid genomic insults and to prevent exhaustion caused by excessive proliferation. 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. Olivieri, J., Dehghannasiri, R., Wang, P. L., Jang, S., de Morree, A., Tan, S. Y., Ming, J., Wu, A., Consortium, T., Quake, S. R., Krasnow, M. A., Salzman, J. TACH101, a first-in-class pan inhibitor of KDM4 histone lysine demethylases. Alzheimer's disease (AD) is a progressive neurodegenerative disease observed with aging that represents the most common form of dementia. Cytoplasmic sequestration of the p53 tumor suppresser protein has been proposed as a mechanism involved in abolishing p53 function. View details for Web of Science ID A1995RY96700021. However, the consequences of the underlying gene-dosage imbalance on adult tissues remain poorly understood. View details for Web of Science ID A1992GX27300015. The inhibitory effect on F-MEL differentiation appeared to be independent of the early decline in c-myc transcripts which were normally regulated in all cases examined. Temporary expression of wild-type p53 activity in the absence of drug treatment caused some loss of clonogenicity, although the magnitude of this cytotoxic effect was small compared with the level of cell kill obtained by treatment with cytotoxic drugs for similar periods of time, indicating that HT29 cells are not highly sensitive to induction of programmed cell death by wild-type p53. The data are consistent with formation of a core particle on one or the other of the repeated enhancer sequences. To test this hypothesis, murine erythroleukemia cells were transfected with bcl-XL and p53ts. In 2007, he became the Director of the Royal United Services Institute. Inhibition of TLR2, its co-receptor CD14, or its downstream targets MYD88 and IRAK1 inhibits growth of human breast cancers in vitro and in vivo. Here we describe c-myb-transformed MEL clones which undergo delayed expression of the exogenous c-myb following 3-5 days of culture in DMSO. Dr. Jim Clarke is an Adjunct Professor of Civil and Environmental Engineering and an Adjunct Professor of Earth and Environmental Sciences at Vanderbilt University. 3-7), attempts to identify tumor suppressors within this band have been unsuccessful. An interleukin-6 family member, interleukin-11 is identified as a secondary target of twinfilin 1 in the microRNA-30c signalling pathway. Zarnegar, M. A., Reinitz, F. n., Newman, A. M., Clarke, M. F. CDX2 as a Prognostic Biomarker in Colon Cancer. Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2; also known as HER-2/neu), is indicated for the treatment of women with either early stage or metastatic HER2(+) breast cancer. 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. This is an overview of the elements and molecules involved in p53 nucleocytoplasmic transportation. Until 2001 he was Deputy Vice-Principal and Director for Research Development at King's College London, where he remains a Visiting Professor. Analysis of the surface molecule repertoire of EpCAM(high)/CD44+ cells led to the identification of CD166 as an additional differentially expressed marker, useful for CSC isolation in three of three CRC tested. Recent studies elucidated the presence of cancer stem cells that have the exclusive ability to regenerate tumors. Treatment-related mortality was 10%. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P=0.002). Here we describe two such clones and report that one of them transforms NIH-3T3 cells. It has been viewed by tens of millions of people around the world, including in China, where Sandel was named the "most . Indomethacin (4 x 10(-4) M) and ETYA (2 x 10(-5) M) did inhibit oxygen utilization and superoxide production. Hematopoietic cells exposed to the suicide vectors were able to reconstitute the bone marrow of mice exposed to lethal doses of y-irradiation. One such cDNA clone, KT1, was isolated and its nucleotide sequence was determined. Vorperian, S. K., Moufarrej, M. N., Tabula Sapiens Consortium, Quake, S. R., Jones, R. C., Karkanias, J., Krasnow, M., Pisco, A. O., Quake, S. R., Salzman, J., Yosef, N., Bulthaup, B., Brown, P., Harper, W., Hemenez, M., Ponnusamy, R., Salehi, A., Sanagavarapu, B. The lactate/glucose and ammonia/glutamine yield coefficients, however, remained invariant at about 1.9 and 1.0 mol/mol, respectively, under all medium perfusion conditions. Comparing ChIP results for two modified histone protein targets, we showed our automated microfluidic ChIP (AutoChIP) from 2,000 cells to be comparable to that of conventional ChIP methods using 50,000-500,000 cells. View details for Web of Science ID A1995TE58500016. In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein-negative colon cancers than among the 276 (87.9%) with CDX2 protein-positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P=0.003). Three seminoma patients remain progression-free. View details for DOI 10.1126/science.aax0249. The AKR/J chromosome 17 locus was not sufficient to increase HSC frequencies when bred onto a C57BL background. C-myb is involved in regulating normal human hematopoiesis, and inhibits dimethyl sulfoxide-induced differentiation of Friend murine erythroleukemia (F-MEL) cells. Cai, S., Kalisky, T., Dalerba, P., Clarke, M., Stanford Univ. Control experiments show that positioning is not due to the 21-bp repeats or to end effects. 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. Mcl1, Tel/Etv6, Gfi1, Pten and Stat5) have been identified. High-dose chemotherapy (HDCT) and autologous bone marrow transplantation (BMT) is frequently used to treat patients with metastatic cancer including breast cancer and neuroblastoma. 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. While the class is nonetheless challenging, Professor Clark does his best to help all students pass. View details for Web of Science ID 000079323200036. Zabala, M., Lobo, N. A., Seoane, J. Metastasis remains a significant challenge in treating cancer. Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. To explore the possible role of c-sis expression in HTLV-induced disease, we have obtained cDNA clones of c-sis from HUT-102 cells. Both fragments formed complexes with electrophoretic mobilities of nucleosomes containing the appropriate length of DNA. In six of seven tumors examined, Thy1+CD24+ cancer cells, which constituted approximately 1%-4% of tumor cells, were highly enriched for cells capable of regenerating new tumors compared with cells of the tumor that did not fit this profile ("not-Thy1+CD24+"). His drumming was basic and, for the most part, appropriate for the Byrds' needs, although he was . 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. Because of the unusual findings of apparently inappropriate HLA antigens in HTLV infected cells, we had previously looked for rearrangement of class I-related genes in HTLV infected cells but failed to find any. 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. We discuss possible functional consequences of such nucleosome positioning. View details for DOI 10.1016/j.stem.2009.05.019, View details for Web of Science ID 000269511900010. 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). Usp16 contributes to somatic stem-cell defects in Down's syndrome. AKR/J mice had significantly higher frequencies and numbers of both HSCs and restricted progenitors in their bone marrow than C57BL/Ka-Thy-1.1 mice. C-myb, the normal cellular homolog of the retroviral transforming gene v-myb, encodes a nuclear, transcriptional regulatory protein (p75c-myb). 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 000173193700014. View details for Web of Science ID 000075125200067. 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. Our study demonstrates that microRNA-30c is transcriptionally regulated by GATA3 in breast tumours. 444 Hutchison (585) 275-3432 michael.clark@rochester.edu. View details for Web of Science ID 000308928300005, View details for Web of Science ID 000318009801791. Further investigation will reveal whether this translates to improved therapy in the future. 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. 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. According to this second scenario, tumors act as caricatures of their corresponding normal tissues and are sustained in their growth by a pathological counterpart of normal adult stem cells, cancer stem cells. View details for DOI 10.1016/j.patbio.2006.01.004, View details for Web of Science ID 000236287600008. He has a long-standing interest in the impact of fire upon fauna. Hosen, N., Clarke, M. F., Weissman, I. L. Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. View details for Web of Science ID 000178077600006. Northstar is a useful tool to assign known and novel cell type and states in the age of cell atlases. GSE professors bring the latest advances in the social sciences, technology and teacher preparation to the field of education. The main battle tanks have a maximum speed of around 43.5mph and a range of . These data suggest that the late fall in c-myb levels may be required in order for differentiation to occur. Dontu, G., Abdallah, W. M., Foley, J. M., Jackson, K. W., Clarke, M. F., Kawamura, M. J., Wicha, M. S. New oncolytic adenoviruses with hypoxia- and estrogen receptor-regulated replication. View details for Web of Science ID 000345777300014. These data suggest that the c-myb protooncogene encodes alternately spliced mRNA species with opposing effects on differentiation. Liu, H., Bockhorn, J., Dalton, R., Olopade, O. F., Clarke, M. F., Greene, G. L. MicroRNAs regulating breast cancer stem cells and metastasis. Upon transfer to 32.5 degrees C, these G1 synchronized cell populations quickly lost viability. 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. On the basis of the wild-type adenovirus type 5, we have constructed a conditionally replicative adenovirus (Ad5ERE2) in which the E1a and E4 promoters have been replaced by a portion of the pS2 promoter containing two estrogen-responsive elements (EREs). 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). These results demonstrate that Bcl-XL is capable of protecting cells from p53-mediated apoptosis, and suggest a possible mechanism by which tumors expressing Bcl-XL are able to partly overcome the tumor suppressor functions of p53. View details for Web of Science ID 000182941000008. The effect of these changes on protein function is currently unknown. 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. Knockdown of KIT decreased proliferation of colon cancer cell lines and growth of xenograft tumors in mice compared with control cells. Murine RV EW robustly activated type I IFNs and several antiviral genes (IFN-stimulated genes) in the intestine by bulk analysis, the source of induced IFNs primarily being hematopoietic cells. Clarke, M. F., Clevers, H., Eaves, C. J., Weinberg, R. A., Rajasekhar, V. K. Quantitative assessment of single-cell RNA-sequencing methods. - Associate Professor: Business Management He is the Karel and Avice Beekhuis Professor in Cancer Biology and Associate Director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine. Director, Teaching & Learning. The metabolic and secretory characteristics of NIH-3T3 fibroblasts transfected with a cDNA encoding human granulocyte-macrophage colony stimulating factor (GM-CSF) were examined as a function of the culture medium exchange schedule.