View details for Web of Science ID A1995TF89100042. 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. View details for Web of Science ID A1994PC47400008. All of the DR alpha DNA sequences detected by a cloned DR alpha cDNA probe are contained in a BglII fragment which varies slightly in size (4.0 to 4.8 kilobases) from one individual to another. Stimulation of trastuzumab-activated human NK cells with an agonistic mAb specific for CD137 killed breast cancer cells (including an intrinsically trastuzumab-resistant cell line) more efficiently both in vitro and in vivo in xenotransplant models of human breast cancer, including one using a human primary breast tumor. 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. 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. In murine leukemia models induced by P210BCR/ABL or TEL/PDGFbetaR + AML1/ETO, Bmi-1 was not overexpressed in leukemic HSCs, despite the increase in the HSC numbers. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. In this study, we report that miR-142 efficiently recruits the APC mRNA to an RNA-induced silencing complex, activates the canonical WNT signaling pathway in an APC-suppression dependent manner, and activates the expression of miR-150. 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. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. More. However, the identity and function of cells expressing EMT-associated genes in normal murine mammary gland homeostasis and human breast cancer still remains under debate. Differential regulation of medium versus serum perfusion demonstrated that increased NIH-3T3 cell metabolism was directly proportional to the serum flux to which the cells were exposed. Finally, questions regarding p53 cellular trafficking will also be discussed. CHUCK, A. S., Clarke, M. F., Palsson, B. O. bcl-x(s) gene therapy induces apoptosis of human mammary tumors in nude mice. Since only a portion of the cells in culture expressed Ig light chains, experiments were carried out to exclude the possibility that the cultures were not a mixture of B and T or non-B cells. The aim of the present study was to determine the effects of Bcl-xS expression on the viability of NB cells. 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. 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. (2002) demonstrate that the CED-1 homolog, Slug, is a key regulator of apoptosis in the response of early hematopoietic progenitors to gamma radiation. View details for Web of Science ID 000079323200036. A., Patsialou, A., Qian, D., Lin, J., Wen, S., Chang, Y., Bachmann, M. H., Shimono, Y., Dalerba, P., Adorno, M., Lobo, N., Bueno, J., Dirbas, F. M., Goswami, S., Somlo, G., Condeelis, J., Contag, C. H., Gambhir, S. S., Clarke, M. F. Rothenberg, M. E., Clarke, M. F., Diehn, M. DLL4 Blockade Inhibits Tumor Growth and Reduces Tumor-Initiating Cell Frequency. We have examined the respiratory burst and arachidonic acid oxygenation that accompany phagocytosis in macrophages. 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. Adjunct Associate Professor Jon Womersley. Room 424:1 Advanced Engineering Building (49) . A., Stelzer, Y., Luong, A. V., Isobe, T., Zarnegar, M. A., Watanabe, N., Antonana, S., Lam, J., Qian, D., Sikandar, S. S., Kuo, A. H., Heitink, L. S., Shimono, Y., Scheeren, F. A., Cai, S., Hisamori, S., Sahoo, D., Dirbas, F. M., Somlo, G., Jaenisch, R., Christina, C., Clarke, M. F. Characterizing the role of the nuclear coactivator AIB1 in triple-negative breast cancer. The expression of the KT1 UCR is unique to HUT102. 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. Here we show that bone marrow cells from mice deficient in three genes genetically downstream of Bmi1--p16Ink4a, p19Arf and Trp53 (triple mutant mice; p16Ink4a and p19Arf are alternative reading frames of the same gene (also called Cdkn2a) that encode different proteins)--have an approximately 10-fold increase in cells able to reconstitute the blood long term. Mandel, Michael - Associate Professor: Computer and Information Science Manlow, Veronica B. 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. We performed the first genome-wide expression analysis directly comparing the expression profile of highly enriched normal human hematopoietic stem cells (HSC) and leukemic stem cells (LSC) from patients with acute myeloid leukemia (AML). In addition, through targeting the cancer stem cell and its dysregulated self-renewal, our therapies for treating cancer are likely to improve. This cell line contains a wild-type p53 gene and is an ideal model for studying the mechanism of IR resistance in this disease. Replication-defective retroviruses are frequently used as gene carriers for gene transfer into target cells. Bockhorn, J., Yee, K., Chang, Y., Prat, A., Huo, D., Nwachukwu, C., Dalton, R., Huang, S., Swanson, K. E., Perou, C. M., Olopade, O. I., Clarke, M. F., Greene, G. L., Liu, H. Innate immune response to homologous rotavirus infection in the small intestinal villous epithelium at single-cell resolution. My research is located in three overlapping fields: (a) linguistic and cultural transfer from Mediterranean Antiquity to the medieval European vernaculars; (b) comparative study of epic and heroic narrative traditions, especially in Greek, Latin, and Babylonian, and of their Celtic and Germanic successors and analogues; (c) semantic 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). 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. 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. This apparent paradox is the focus of our interest. 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. These sequences, when compared with those previously reported for the human c-myb gene, reveal an alternative splicing process that generates at least four forms of the c-myb message. 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. It was found that a single mutation of Arg-306 resulted in the defect of p53 nuclear import. 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. Treatment of these T-cells with 5-azacytidine resulted in the induction of DR surface antigen expression, the appearance of DR alpha mRNA, and the partial demethylation of the DR alpha DNA sequences. DP16-1 cells which were untransfected or co-transfected with wtp53 and bcl-2 displayed characteristics of cells undergoing necrosis. Stromal Gli2 activity coordinates a niche signaling program for mammary epithelial stem cells. Pancreatic cancer cells with the CD44(+)CD24(+)ESA(+) phenotype (0.2-0.8% of pancreatic cancer cells) had a 100-fold increased tumorigenic potential compared with nontumorigenic cancer cells, with 50% of animals injected with as few as 100 CD44(+)CD24(+)ESA(+) cells forming tumors that were histologically indistinguishable from the human tumors from which they originated. President Biden has reaffirmed the U.S. commitment to the North Atlantic Treaty Organization (NATO) and collective defense and has stated that a strong European Union is in the U.S. interest. 2010). We thus identify stromal cells as cellular coordinators of colon inflammation and suggest their pharmacologic manipulation as a potential means to treat colitis. X-ray irradiated cells expressing wtp53 displayed microscopic and biochemical characteristics consistent with cell death due to apoptosis. 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. 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. View details for DOI 10.1016/j.gde.2003.11.007, View details for Web of Science ID 000188978200008. Recent observations indicate that, in several types of human cancer, only a phenotypic subset of cancer cells within each tumor is capable of initiating tumor growth. Their scholarship is deepening our understanding of learning while changing policy and practice. 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. It has 234 amino acids consisting of a central RGS box and short divergent NH(2) and COOH termini. Transformation is a complex cellular process that requires several genetic abnormalities. Unfortunately, although chemotherapy and/or radiation therapy can sometimes shrink tumors, metastatic cancers of epithelial origin are essentially incurable. View details for DOI 10.1038/s41598-020-71805-1. 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. View details for DOI 10.1196/annals.1349.012, View details for Web of Science ID 000230894100011, View details for Web of Science ID 000225161400025. The efficiency of gene therapy strategies against cancer is limited by the poor distribution of the vectors in the malignant tissues. 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. Surface markers that displayed intratumor heterogeneous expression among epithelial cancer cells were selected for cell sorting and tumorigenicity experiments. View details for DOI 10.1016/j.cell.2009.07.011, View details for Web of Science ID 000268771900022, View details for PubMedCentralID PMC2731699. This includes loss of a portion of the region involved in transcription activation as well as a separate highly conserved domain. Cytoplasmic sequestration of the p53 tumor suppresser protein has been proposed as a mechanism involved in abolishing p53 function. Alzheimer's disease (AD) is a progressive neurodegenerative disease observed with aging that represents the most common form of dementia. Results The transcription factor CDX2 ranked first in our screening test. Schaum, N. n., Lehallier, B. n., Hahn, O. n., Plovics, R. n., Hosseinzadeh, S. n., Lee, S. E., Sit, R. n., Lee, D. P., Losada, P. M., Zardeneta, M. E., Fehlmann, T. n., Webber, J. T., McGeever, A. n., Calcuttawala, K. n., Zhang, H. n., Berdnik, D. n., Mathur, V. n., Tan, W. n., Zee, A. n., Tan, M. n., Pisco, A. O., Karkanias, J. n., Neff, N. F., Keller, A. n., Darmanis, S. n., Quake, S. R., Wyss-Coray, T. n. Northstar enables automatic classification of known and novel cell types from tumor samples. Imatinib inhibited growth of KIT(+) colon cancer organoids in culture and growth of xenograft tumors in mice. 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. van Weele, L. J., Scheeren, F. A., Cai, S. n., Kuo, A. H., Qian, D. n., Ho, W. H., Clarke, M. F. Single-cell transcriptional diversity is a hallmark of developmental potential. 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. These cancerous cells then grow clonally into tumors and eventually have the potential to metastasize. Although neither the visual interpretation nor SUVlean differentiated mature teratoma from necrosis or scar, there were statistically significant differences in the kinetic rate constants K1 and K between mature teratoma and necrosis or scar as follows: K1, 0.113 mL/min/g +/- 0.026 versus 0.036 mL/min/g +/- 0.005 (P < .05); K, 0.005 mL/min/g +/- 0.003 versus 0.0008 mL/min/g +/- 0.0001 (P < .05).FDG PET with kinetic analysis appears to be a promising method for management of disease in patients with GCT after treatment. It has been reported that Lysine-305 is needed for the nuclear import of the p53 protein (Liang et al., 1998). Similarly, tumors contain a minority population of cancer stem cells that maintain the tumor. Growing up on Chicago's South Side in the 1960s and 1970s, Michael Clarke Duncan experienced poverty and crime as an unfortunately normal part of life. Here we implement single-cell PCR gene-expression analysis to dissect the cellular composition of primary human normal colon and colon cancer epithelia. Liu, H., Shimono, Y., Bockhorn, J., Olopade, F., Greene, G., Clarke, M. F. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. His best known works are the script he wrote with American film director Stanley Kubrick for 2001: A Space Odyssey (1968) and the novel of that film. These results suggest that cancers can evolve SE to drive CD47 overexpression to escape immune surveillance. Despite intensive study of p53, the regulation of p53 cellular localization is still poorly understood. In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. 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. However, at later times X-ray irradiated parental DP16-1 cells also had decreased survival compared to the unirradiated control. miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway. Comparison of IRF3 and NF-B induction in STAT1(-/-) mice revealed that murine but not simian RRV mediated accumulation of IkB- protein and decreased transcription of NF-B-dependent genes. Screening test and bcl-2 displayed characteristics of cells undergoing necrosis several genetic abnormalities to improve p53 (! 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