Han, J. S., Nunez, G., Wicha, M. S., Clarke, M. F. Prevention of fluorodeoxyuridine-induced cytotoxicity and DNA damage in HT29 colon carcinoma cells by conditional expression of wild-type p53 phenotype. View details for Web of Science ID 000168861600008. Human tumors where evidence of cancer stem cells has been published include tumors of the breast, brain, pancreas, head and neck, and colon. 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. 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. In both breast cancers and central nervous system tumors, cancer cells differ in their ability to form tumors. Bmi-1 was expressed at its highest levels in undifferentiated leukemia cells. 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. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. These results suggest that cancers can evolve SE to drive CD47 overexpression to escape immune surveillance. To do so, we used breast tumors of the mouse mammary tumor virus (MMTV)-Wnt-1 mice. He is so driven about his work and is so charismatic to his students. MicroRNAs (miRNAs) are important regulators of stem and progenitor cell functions. The expression of the E1A gene in both viruses is controlled by a minimal dual-specificity promoter that responds to estrogens and hypoxia. "Bulk" measurements of antiviral innate immune responses from pooled cells yield averaged signals and do not reveal underlying signaling heterogeneity in infected and bystander single cells. Amy Smith Berylson Professor of Materials Science and Professor of Chemistry & Chemical Biology. We observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it in select cell types. The number of HSCs in the fetal liver of Bmi-1-/- mice was normal. 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. Using gene transfer technology, we can now deliver genes that accomplish this goal. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. Here, a systematic approach using bioinformatics and array hybridization techniques to analyze gene expression profiles in HSCs is described. 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. 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. Knockdown of KIT decreased proliferation of colon cancer cell lines and growth of xenograft tumors in mice compared with control cells. The hair color is Light brown and the eye color is Blue. View details for DOI 10.1002/1878-0261.13220, View details for DOI 10.1038/s41587-022-01293-3. Intriguingly, overexpression of p53 could reverse the inherent IR resistance of Shep-1 cells. These results indicated the involvement of cis-acting sequences in the regulation of p53 subcellular localization. Michael Clarke is a UK academic and "terror expert". Many of these mutations affect cell proliferation and survival. These data suggest that the late fall in c-myb levels may be required in order for differentiation to occur. Dr. Michael F. Clarke is the Associate Director of the Stanford Institute for Stem Cell and Regenerative Medicine. Furthermore, these approaches are not feasible for primary tumor cells that cannot survive tissue culture conditions or that may change phenotype in rats. View details for DOI 10.1038/s41586-018-0590-4, View details for DOI 10.1126/science.aal3485, View details for Web of Science ID 000399540100053. The conditional expression of lethal genes in tumor cells is a promising gene therapy approach for the treatment of cancer. 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. Previous studies have shown that blocking DLL4 signaling reduced tumor growth by disrupting productive angiogenesis. 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. This article discusses the role of the Bcl-2 family of proteins in the light of these findings. This effect is the same as that of Lys-305 mutation. 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. However, the consequences of the underlying gene-dosage imbalance on adult tissues remain poorly understood. B., Alizadeh, A. 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. 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. Here, we have shown that upon encountering trastuzumab-coated, HER2-overexpressing breast cancer cells, human NK cells become activated and express the costimulatory receptor CD137. In many tissues, a cellular hierarchy exists in which a small population of stem cells is responsible for the production of the mature cells of the organ. The nucleotide sequence of a transforming human c-sis complementary DNA shows an open reading frame 723 base pairs in length located downstream from an in-phase terminator thymine-guanine-adenine codon. View details for Web of Science ID A1992JB22100010. View details for Web of Science ID A1991GR93700016. Recently, various new players that regulate HSC maintenance (e.g. We demonstrate that nonadherent mammospheres are enriched in early progenitor/stem cells and able to differentiate along all three mammary epithelial lineages and to clonally generate complex functional structures in reconstituted 3D culture systems. View details for Web of Science ID 000083623000026. 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. LDV infects specifically mouse macrophages and alters immune system and tumor phenotype. Rachel Ellehuus. These results indicate that addition of combinations of hematopoietic CSFs, together with a rapid medium exchange rate, can provide culture conditions that are suitable for the expansion of the progenitor cell pool and perhaps for the increased survival of hematopoietic stem cells in culture. Clarke, M. F., Gelmann, E. P., Reitz, M. S. RELATION OF RESPIRATORY BURST AND ARACHIDONATE METABOLISM DURING PHAGOCYTOSIS BY GUINEA-PIG ALVEOLAR MACROPHAGES. Most cancers comprise a heterogenous population of cells with marked differences in their proliferative potential as well as the ability to reconstitute the tumor upon transplantation. The AKR/J chromosome 17 locus was not sufficient to increase HSC frequencies when bred onto a C57BL background. Increased levels of Bcl-XL were found in a subset of primary human breast carcinomas, as well as in the breast cancer line, T47D. These data are consistent with the idea that the human T-lymphotropic virus type I LTR contains an enhancer which can activate upstream sequences in cis. With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. A., Issa, J., Clarke, M. F., Look, A. T. Lobo, N. A., Shimono, Y., Qian, D., Clarke, M. F. Cancer stem cells and radiotherapy: New insights into tumor radioresistance. Also, HTLV can be transmitted in vitro to cord blood T-lymphocytes. Hematopoietic stem cells (HSCs) have self-renewal capacity and multilineage developmental potentials. It has been viewed by tens of millions of people around the world, including in China, where Sandel was named the "most . 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. View details for Web of Science ID 000227329300006. DP16-1 cells which were untransfected or co-transfected with wtp53 and bcl-2 displayed characteristics of cells undergoing necrosis. RNA splicing programs define tissue compartments and cell types at single-cell resolution. 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. 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. Chen, E. C., Karl, T. A., Kalisky, T., Gupta, S. K., O'Brien, C. A., Longacre, T. A., van de Rijn, M., Quake, S. R., Clarke, M. F., Rothenberg, M. E. miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway. Expression of wild-type p53 phenotype for 24 hr before FdUrd treatment provided HT29 cells with virtually complete protection from cytotoxicity caused by this drug. Stromal Gli2 activity coordinates a niche signaling program for mammary epithelial stem cells. Sugawara, Y., Zasadny, K. R., Grossman, H. B., Francis, I. R., Clarke, M. F., Wahl, R. L. The nuclear import of p53 is determined by the presence of a basic domain and its relative position to the nuclear localization signal, Role of p53 in the regulation of irradiation-induced apoptosis in neuroblastoma cells. To solve this problem, a new generation of tumor-specific, conditionally replicative adenoviruses is being developed. View details for Web of Science ID A1991EY27300001. Some factors that regulate this process of self-renewal are conserved from fruit fly to humans. Similarly, tumors contain a minority population of cancer stem cells that maintain the tumor. Individual phenotypic cancer cell subsets were purified, and their tumor-initiating properties were investigated by injection in NOD/SCID mice. Nuovo ateismo o neo-ateismo, anche nella grafia neoateismo (in inglese New Atheism), una corrente di pensiero che raccoglie le posizioni promosse da alcuni atei del XXI secolo. 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. Growing evidence suggests that pathways that regulate the self-renewal of normal stem cells are deregulated in cancer stem cells resulting in the continuous expansion of self-renewing cancer cells and tumor formation. In concert with endogenous DMSO-induced globin transcription during MEL cell differentiation, the beta-globin c-myb transcription unit of the transfected plasmid is activated after 3-5 days of culture in media containing DMSO. The tumors in these tissues consist of heterogeneous populations of cancer cells that differ markedly in their ability to proliferate and form new tumors. Furthermore, the LTBMCs produced nonadherent colony-forming unit-GM (CFU-GM) for more than 20 weeks. 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). The height of Michael Clarke is in centimeters- 165 cm in meters- 1.65 m in Feet Inches- 5' 5". Liu, H., Bockhorn, J., Dalton, R., Nwachukwu, C., Prat, A., Yee, K., Huang, S., Swanson, K., Perou, C. M., Olopade, O. I., Clarke, M. F., Greene, G. L. MicroRNA-203 restricts the proliferation capacity of normal colon and colon cancer stem cells by regulating the expression of Tcf4. 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. View details for Web of Science ID 000345638500001, View details for DOI 10.1158/1538-7445.AM2014-SY12-04, View details for Web of Science ID 000349910205454, View details for Web of Science ID 000351670400001. We developed a new technique that replaces immunoprecipitation with a simplified chromatin fragmentation and proximity ligation step that eliminates bead purification and washing steps. The p53-independent pathway does not appear to involve apoptosis and occurs at a later time, starting 48 h after X-ray exposure. Park, I. K., He, Y. Q., Lin, F. M., Laerum, O. D., Tian, Q., Bumgarner, R., Klug, C. A., Li, K. J., Kuhr, C., Doyle, M. J., Xie, T., Schummer, M., Sun, Y., GOLDSMITH, A., Clarke, M. F., Weissman, I. L., Hood, L., Li, L. H. A genetic determinant that specifically regulates the frequency of hematopoietic stem cells. Studies have shown that blocking DLL4 signaling reduced tumor growth by disrupting productive angiogenesis ability to proliferate form. 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