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). They discuss the increasing threat of China, the post-Brexit identity of "Global Britain" and how the . Similarly, tumors contain a minority population of cancer stem cells that maintain the tumor. It is likely that targeting cancer cell self-renewal pathways will result in more effective cancer therapies. These results suggest that the activity of some mutant p53 proteins can be functionally modified by exogenous compounds. Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. 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. View details for DOI 10.1038/s41598-020-71805-1. The tumor suppressor protein p53 has been identified as a key regulator of apoptosis in both normal and malignant hematopoietic cells. Usp16 copy number normalization restores normal Wnt activation in Ts65Dn mice models. 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. p16Ink4a deficiency partially reverses the self-renewal defect in Bmi-1-/- neural stem cells. We developed selective anti-human and anti-mouse DLL4 antibodies to dissect the mechanisms involved by analyzing the contributions of selectively targeting DLL4 in the tumor or in the host vasculature and stroma in xenograft models derived from primary human tumors. Sequences within this region were identical to those previously determined for the exons of the normal human c-sis gene. Indomethacin (4 x 10(-4) M) and ETYA (2 x 10(-5) M) did inhibit oxygen utilization and superoxide production. 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). Downregulation of Usp16, either by mutation of a single normal Usp16 allele or by short interfering RNAs, largely rescues all of these defects. Email: charlotte.clarke@ed.ac.uk. 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. Majetl, R., Becker, M. W., Tian, Q., Lee, T. M., Yan, X., Liu, R., Chiang, J., Hood, L., Clarke, M. F., Weissman, I. L. Identification of Conserved Gene Expression Programs in Epithelial Cancer Stem Cells. B-cell lines established from two individuals with T-cell acute lymphocytic leukemia (T-ALL) express HLA-DR antigens, whereas the isogenic T-cells do not. Together, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity. Using these targeted reporter mice, we demonstrated that Bmi-1 is expressed in hematopoietic stem cells (HSCs) at its highest levels and downregulated upon commitment to differentiation. Investigating mechanisms of cancer stern cell radioresistance. This suggested that endogenous Bcl-XL could protect cancer cells from p53-mediated apoptosis. We used a replication-deficient adenoviral vector to transiently overexpress Bcl-xs in MCF-7 human breast cancer cells, which overexpress Bcl-xL. Oncolytic adenoviruses with restricted replication can be produced if the expression of crucial transcription units of the virus is controlled by tissue- or tumor-specific promoters. The tumorigenic cells displayed stem cell-like properties in that they were capable of generating new tumors containing additional stem cells as well as regenerating the phenotypically mixed populations of non-tumorigenic cells present in the original tumor. View details for Web of Science ID A1995TF89100042. Varma, A., ELAWAR, F. Y., Palsson, B. O., Emerson, S. G., Clarke, M. F. MALIGNANT TRANSFORMATION OF NIH 3T3 FIBROBLASTS BY HUMAN C-SIS IS DEPENDENT UPON THE LEVEL OF ONCOGENE EXPRESSION. Rachel Ellehuus. BIO-IMEB - Biofilms in Industry, Medicine & Environmental Biot, Galway, Ireland, 9-14 August 2003. In contrast to cells in G1, cells cultured at 32.5 degrees C for prolonged periods during S phase and G2/M, and then returned to 37.5 degrees C, did not become committed to cell death. The in vitro culture of mouse bone marrow (Dexter cultures) has allowed a detailed analysis of the biology of murine hematopoiesis. We have designed a microfluidic device to perform sensitive ChIP analysis on low cell numbers in a rapid, automated fashion while preserving the specificity of the assay. Purified RGS18 interacts with the alpha subunit of both G(i) and G(q) subfamilies. 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. Bcl11b maintains the long-term mammary stem cell and is crucial for drug resistance in breast cancer. We examined the effect of this limited adenovirus replication in vitro and in vivo. Recently, it has become apparent that some oncogenes and tumor suppressor genes also regulate self-renewal, the process by which stem cells maintain themselves. We thus identify stromal cells as cellular coordinators of colon inflammation and suggest their pharmacologic manipulation as a potential means to treat colitis. Epigenetic regulation of normal and cancer stem cells, Neurobiology: At the root of brain cancer, Chronic myelogenous leukemia - Identifying the hydra's heads, Therapeutic implications of cancer stem cells. View details for Web of Science ID A1995TE58500016. The induced p53 is functional as p53-responsive genes (Waf-1 and MDM-2) are appropriately induced following IR. Metastasis remains a significant challenge in treating cancer. His drumming was basic and, for the most part, appropriate for the Byrds' needs, although he was . This technology may provide a solution to the need for a high sensitivity, rapid, and automated ChIP assay, and in doing so facilitate the use of ChIP for many interesting and valuable applications. Diehn, M., Cho, R. W., Ailles, L., Lam, J. S., Kaplan, M. J., Somlo, G., Weissman, I. L., Clarke, M. F. Implications of Cancer Stem Cells for Tumor Metastasis. The prognostic role of a gene signature from tumorigenic breast-cancer cells. Just months into the Biden-Harris administration, the change in tone, message, and approach to transatlantic relations is palpable. These data suggest that the c-myb protooncogene encodes alternately spliced mRNA species with opposing effects on differentiation. 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. Critically, we found that only streaming and not random migration of single cells was significantly correlated with proximity to vessels, with intravasation and with numbers of elevated circulating tumor cells in the bloodstream. Many cancers overexpress a member of the bcl-2 family of inhibitors of apoptosis. Clarke, M. F., Gelmann, E. P., Reitz, M. S. RELATION OF RESPIRATORY BURST AND ARACHIDONATE METABOLISM DURING PHAGOCYTOSIS BY GUINEA-PIG ALVEOLAR MACROPHAGES. 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. Mandel, Michael - Associate Professor: Computer and Information Science Manlow, Veronica B. The p53-independent pathway does not appear to involve apoptosis and occurs at a later time, starting 48 h after X-ray exposure. G1 arrest at 37.5 degrees C, utilizing either mimosine or isoleucine deprivation, does not lead to rapid cell death. Limiting dilution transplantations of breast epithelial cells devoid of TLR2 or MYD88 revealed a significant decrease in mammary repopulating unit frequency compared with the control. These pathways are commonly repressed in cancer, suggesting a mechanism by which early progenitor cells could gain the ability to self-renew and become malignant with further oncogenic mutations. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. Therefore, to better treat cancer it may be necessary to develop novel methods to overcome the effects of the Bcl-2 family. Hosen, N., Clarke, M. F., Weissman, I. L. Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. 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. Cells that expressed kappa- or lambda-light chains were separated by cell sorting from kappa- or lambda-negative cells and replaced in culture. 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. Liu, H., Bockhorn, J., Dalton, R., Olopade, O. F., Clarke, M. F., Greene, G. L. MicroRNAs regulating breast cancer stem cells and metastasis. Zarnegar, M. A., Reinitz, F. n., Newman, A. M., Clarke, M. F. CDX2 as a Prognostic Biomarker in Colon Cancer. A., Clarke, M. F., Weissman, I. L. MicroRNAs regulate breast cancer stem cells and spontaneous metastases in orthotopic xenograft models. Limited viral replication facilitates greater penetration of virions into tissue and can improve gene transfer. They were introduced into the E4 region of AdEHT2 and AdEHE2F, respectively. Dole, M. G., Clarke, M. F., Holman, P., Benedict, M., Lu, J. Y., Jasty, R., EIPERS, P., Thompson, C. B., Rode, C., Bloch, C., Nunez, G., Castle, V. P. Strategy for identifying genes responsible for hemotopoietic stem cell homeostasis. 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. This suggests that expression of DR antigens also can be modulated post-transcriptionally. We have examined the respiratory burst and arachidonic acid oxygenation that accompany phagocytosis in macrophages. Metastasis is the main cause of death in breast cancer patients. View details for DOI 10.1016/j.cell.2009.07.011, View details for Web of Science ID 000268771900022, View details for PubMedCentralID PMC2731699. Ad5ERE2 is able to kill ER(+) human breast cancer cell lines as efficiently as the wild-type virus, but has decreased capacity to affect ER(-) cells. All measured metabolic rates increased with increased medium exchange rates and accelerated sharply between exchange rates of 3.5/week and 7/week. Bcl11b(high) cells are enriched for cells that can regenerate mammary glands in secondary transplants. Automated microfluidic chromatin immunoprecipitation from 2,000 cells. Previous studies have proposed that epithelial to mesenchymal transition (EMT) in breast cancer cells regulates metastasis, stem cell properties and chemo-resistance; most studies were based on in vitro culture of cell lines and mouse transgenic cancer models. 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. Disruption of the regulation of self-renewal results in cancer. Patients were eligible for a second cycle if disease progression was absent and performance status allowed. Morrison, S., Park, I., Qian, D. L., Jerabek, L., Weissman, I., Clarke, M. F. Retroviral infection is limited by Brownian motion. James Mallet (* 1955), Evolutionsbiologe und Entomologe. Ailles, L., Prince, M., Joshua, B., Doweck, I., Kaplan, M., Clarke, M., Weissman, I. Arthur Thomas Malkin (1803-1888), Pionier der Bergsteigerei und Schriftsteller. In the present study, further mutagenesis analyses were carried out between Lys-305 and the major nuclear localization signal (NLS I) of p53. Our studies show that coincident expression of human Bcl-2 protein with p53 prolongs survival of murine erythroleukemia cells. Replication-deficient viral vectors are currently being used in gene transfer strategies to treat cancer cells. 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. Currently being used in gene transfer by exogenous compounds of apoptosis of IFN in... 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Methods to overcome the effects of the Bcl-2 family long-term mammary stem cell and is crucial for resistance... & amp ; Environmental Biot, Galway, Ireland, 9-14 August 2003 Environmental Biot, Galway, Ireland 9-14... Replaced in culture and can improve gene transfer by exogenous compounds death breast. Single RV-infected and bystander intestinal epithelial cells ( IECs ) minority population of stem...

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