His interest is in Stem Cell Biology. We focused our analysis of gene expression on RNA from primitive leukemia-initiating cells, which harbor 5q deletions, and analyzed 12 genes within the CDR that are expressed by normal hematopoietic stem cells. in Pounds- 159 lbs. The expression of the E1A gene in both viruses is controlled by a minimal dual-specificity promoter that responds to estrogens and hypoxia. Previous groups have shown that CD24medCD49fhigh cells enriched for long-lived mammary epithelial cells can be serially transplanted.METHODS: Flow cytometry-based enrichment of distinct phenotypic populations was assessed for their gene expression profiles and functional proliferative attributes in vitro and in vivo.RESULTS: Here, we show Thy-1 is differentially expressed in the CD24medCD49fhigh population, which allowed us to discern two functionally different populations. The telomerase core promoter failed to block the replication of the virus in telomerase-negative cells. Herein, we present a discussion around the issues facing treatment of patients with CRCliver metastases, including the relationship of discretegene signatures with prognosis. in Management and an M.S. To test this hypothesis, murine erythroleukemia cells were transfected with bcl-XL and p53ts. When a promoter containing these elements is used to control the expression of the pro-apoptotic gene harakiri, the induction of cell death can be activated by estrogens and hypoxia, and inhibited by antiestrogens such as tamoxifen. 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. 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. Fundamentally, the system is the paradigm of a complex interactive tissue, in which the proliferation and regulated differentiation of one parenchymal cell type (the hematopoietic stem cell) is governed by the surrounding stromal cells. 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. Treatment-related mortality was 10%. This article discusses the role of the Bcl-2 family of proteins in the light of these findings. RNA splicing programs define tissue compartments and cell types at single-cell resolution. Director, Teaching & Learning. 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. Solid tumors such as breast cancers contain heterogeneous populations of neoplastic cells. Utilizing computer-assisted integration techniques, we have theoretically simulated culture cell production kinetics to help identify factors that may be responsible for culture decay, as well as to suggest possible means of improving culture longevity. Identification of a novel microRNA-mediated pathway that regulates chemoresistance in breast cancer will facilitate the development of novel therapeutic strategies. Using terminal transferase-mediated dUTP-digoxigenin nick end labeling, we observed apoptotic cells at sites of bcl-xs adenoviral injection. Jasty, R., Lu, J. Y., Irwin, T., Suchard, S., Clarke, M. F., Castle, V. P. Cooperation of a single lysine mutation and a C-terminal domain in the cytoplasmic sequestration of the p53 protein, A method of limited replication for the efficient in vivo delivery of adenovirus to cancer cells. In breast cancer, while a subset of cells with epithelial and mesenchymal phenotypes have stem cell activity, in many cells that have lost epithelial characteristics with increased expression of mesenchymal genes, have decreased tumor-initiating capacity and plasticity. View details for Web of Science ID 000079323200036. We identify two distinct super-enhancers (SEs) associated with CD47 in certain cancer cell types. The calculated molecular weight of RGS18 is 27,610 and the isoelectric point is 8.63. 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. However, the consequences of the underlying gene-dosage imbalance on adult tissues remain poorly understood. . Bystander cells did not display enhanced type I IFN transcription but had elevated levels of certain IFN-stimulated genes, presumably in response to exogenous IFNs secreted from immune cells. View details for Web of Science ID 000168861600008. A., Chen, L., Levy, R. Removal of lactate dehydrogenase-elevating virus from human-in-mouse breast tumor xenografts by cell-sorting. All measured metabolic rates increased with increased medium exchange rates and accelerated sharply between exchange rates of 3.5/week and 7/week. 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. 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. View details for DOI 10.1016/j.gde.2003.11.007, View details for Web of Science ID 000188978200008. Following release into G1, cells became irreversibly committed to cell death after 4 h at 32.5 degrees C. Commitment to cell death correlated with the first appearance of fragmented DNA. A temperature-sensitive mutant of murine p53 (p53Val-135) and/or bcl-2 was transfected into murine erythroleukemia cells (MEL, DP16-1, which are null in p53). View details for Web of Science ID A1994NT46100030. He has a long-standing interest in the impact of fire upon fauna. He is a Professor at La Trobe University in Melbourne, Victoria, where he has worked since 1992. 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. 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. Comparing the expression signature of normal HSC to that of LSC, we identified 3,005 differentially expressed genes. These chemically reactive forms of biotin produced derivatives biotinylated at amine or carboxyl groups, respectively. Cells that expressed kappa- or lambda-light chains were separated by cell sorting from kappa- or lambda-negative cells and replaced in culture. The regulation of hematopoietic stem cell (HSC) homeostasis is not well understood. View details for DOI 10.1038/s41586-020-2496-1, View details for Web of Science ID 000485326200019, View details for DOI 10.1158/1538-7445.SABCS18-SY17-02, View details for Web of Science ID 000488129901140, View details for Web of Science ID 000453773601250. We have studied the ability of c-myc and bcl-2 oncogenes to modulate p53 function. Al-Hajj, M., Becker, M. W., Wichal, M., Weissman, I., Clarke, M. F. Bmi1, stem cells, and senescence regulation. Dalerba, P., Dylla, S. J., Park, I., Liu, R., Wang, X., Cho, R. W., Hoey, T., Gurney, A., Huang, E. H., Simeone, D. M., Shelton, A. It has been postulated that there is a link between inflammation and cancer. This system allows one round of viral replication. Within the colon, the Hedgehog protein signal does not act directly on the epithelium itself, but on underlying stromal cells to induce expression of IL-10, an immune-modulatory cytokine long known to suppress inflammatory intestinal damage. 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). We have previously shown that two human T-cell lines (HSB and 8402) derived from patients with childhood T-cell ALL (T-ALL) do not synthesize detectable mRNA for HLA-DR alpha. Restoration of CTNNA1 expression in HL-60 cells resulted in reduced proliferation and apoptotic cell death. In approaching the bone marrow culture system, we recognize the critical role that hematopoietic growth factors (HGFs) play in hematopoiesis. Furthermore, the oxygenation of arachidonic acid requires little of the oxygen consumed by phagocytosing alveolar macrophages. To investigate the possible role of Bmi-1 in other cell types that also self-renew, we generated Bmi-1-green fluorescent protein (GFP)-knock-in mice, in which GFP was expressed under the endogenous transcriptional regulatory elements of the Bmi-1 gene. 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. This promoter induces transcriptional activation of the E1a and E4 units in response to estrogens in cells that express the ERs. This suggests that to affect HSC frequencies, the product(s) of this locus likely depend on interactions with unlinked modifying loci. This effect was associated with a loss of the G1 specificity of p53-mediated cell cycle arrest. Furthermore, in human tissues overexpression of USP16 reduces the expansion of normal fibroblasts and postnatal neural progenitors, whereas downregulation of USP16 partially rescues the proliferation defects of Down's syndrome fibroblasts. Strategies that enhance the activity of ADCC effectors, including NK cells, may improve the efficacy of trastuzumab. Ailles, L., Prince, M., Joshua, B., Doweck, I., Kaplan, M., Clarke, M., Weissman, I. Following synchronization by density arrest, transfected cells released into G1 at 32.5 degrees C were found to lose viability more rapidly than did randomly growing cultures. . 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. 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. Here we investigate the roles of these three proteins in the regulation of self-renewal and proliferation of mammary epithelial cells. In 2007, he became the Director of the Royal United Services Institute. 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). These results indicate that the CSD can regulate p53 nuclear import by controlling access of the NLS to importin alpha binding. 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. 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. Stem cells in normal breast development and breast cancer. View details for Web of Science ID A1994PC47400008. By focusing on the biology of CoCSC, major resistance mechanisms to specific chemotherapeutic agents can be attributed to specific genes, thereby suggesting avenues for improving cancer therapy. Human tumors where evidence of cancer stem cells has been published include tumors of the breast, brain, pancreas, head and neck, and colon. In order to better understand HSC self-renewal, we need to understand how these pathways are coordinated. Its expansion is a tightly regulated process, fueled by the mammary stem cells and these cells' unique property of self-renewal. The data are consistent with formation of a core particle on one or the other of the repeated enhancer sequences. Mandel, Michael - Associate Professor: Computer and Information Science Manlow, Veronica B. bcl-x is a member of the bcl-2 family of genes and by alternative splicing gives rise to two distinct mRNAs: bcl-xL and bcl-xS. The productivity of cultures exposed to conCM for 4 weeks dropped significantly when unsupplemented medium was used for the latter 4 weeks of culture. 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. 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. It is most highly expressed in bone marrow followed by fetal liver, spleen, and then lung. 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). The prognostic role of a gene signature from tumorigenic breast-cancer cells. Taken together, these data demonstrate that cells within the CD44(+) population of human HNSCC possess the unique properties of cancer stem cells in functional assays for cancer stem cell self-renewal and differentiation and form unique histological microdomains that may aid in cancer diagnosis. View details for Web of Science ID 000255592400041, View details for Web of Science ID 000246136200023. Pagination. The United States has always regarded certainly jihadist terrorism . F-MEL clones expressing the highest levels of the human c-myb mRNA differentiate poorly in response to dimethyl sulfoxide. Knockdown of KIT decreased proliferation of colon cancer cell lines and growth of xenograft tumors in mice compared with control cells. In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. The plasmid vector contains simian virus 40-derived promotor, splice, and polyadenylation sequences as well as a transcription unit for a dihydrofolate reductase cDNA. However, the underlying molecular mechanisms are poorly characterized. By complementation of the E1a protein in trans, Ad5ERE2 allows restricted replication of a conventional E1a-deleted adenoviral vector. As we continue to advance clinically and technologically in the field of colorectal tumor biology, ourgoal should be continuedrefinement of predictive and prognostic studiesto decrease recurrence after curative resection and minimize treatment toxicity to patients through a tailoredmultidisciplinary approach to cancer care. Taken together, these results suggest that USP16 has an important role in antagonizing the self-renewal and/or senescence pathways in Down's syndrome and could serve as an attractive target to ameliorate some of the associated pathologies. Other mutations between Arg-306 and NLS I have no effect on the nuclear import of p53. Following his specialty training in medical oncology at Royal Prince Alfred and Westmead Hospitals, Professor Boyer was a Research Fellow and Clinical Fellow at the Ontario Cancer Institute and Princess Margaret Hospital in Toronto, Canada, where he completed his PhD on cell biology. 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. View details for DOI 10.1016/j.jviromet.2011.02.015, View details for Web of Science ID 000290836400014, View details for PubMedCentralID PMC3086718, View details for DOI 10.1158/1538-7445.AM2011-1582, View details for Web of Science ID 000209701302286, View details for Web of Science ID 000289796200068. A spacer between this basic domain and NLS I is necessary for the entrance of p53 into the cell nucleus. Reply. Il neo-ateismo ritiene che la superstizione, la religione e l'irrazionalismo non dovrebbero essere tollerati, e si propone di contrastarli . View details for Web of Science ID 000173193700014. Increased levels of Bcl-XL were found in a subset of primary human breast carcinomas, as well as in the breast cancer line, T47D. 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. 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. Zabala, M., Lobo, N. A., Seoane, J. Arthur C. Clarke, in full Sir Arthur Charles Clarke, (born December 16, 1917, Minehead, Somerset, Englanddied March 19, 2008, Colombo, Sri Lanka), English writer, notable for both his science fiction and his nonfiction. 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. Clarke, M. F., Dick, J. E., Dirks, P. B., Eaves, C. J., Jamieson, C. H., Jones, D. L., Visvader, J., Weissman, I. L., Wahl, G. M. A self-renewal assay for cancer stem cells. Mini Bio (1) Michael Clarke Duncan was born on December 10, 1957 in Chicago, Illinois. Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. We used a replication-deficient adenoviral vector to transiently overexpress Bcl-xs in MCF-7 human breast cancer cells, which overexpress Bcl-xL. 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. 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. Therefore, functional inhibition of Bcl-2 family members is lethal to many cancer cells. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. Program Affiliations. 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. Palovics, R., Keller, A., Schaum, N., Tan, W., Fehlmann, T., Borja, M., Kern, F., Bonanno, L., Calcuttawala, K., Webber, J., McGeever, A., Tabula Muris Consortium, Luo, J., Pisco, A. O., Karkanias, J., Neff, N. F., Darmanis, S., Quake, S. R., Wyss-Coray, T., Almanzar, N., Antony, J., Baghel, A. S., Bakerman, I., Bansal, I., Barres, B. 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. Finally, we show evidence that these properties are maintained in the context of an adenoviral vector (AdEHhrk). Hematopoietic stem cell gene therapy holds the promise of being able to treat a variety of inherited and acquired diseases of the hematopoietic stem cell. 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. Stem cells generate the differentiated cell types within many organs throughout the lifespan of an organism and are thus ultimately responsible for the longevity of multicellular organisms. In DNA from the T-cells not expressing DR alpha mRNA, all of the potential HpaII sites within the BglII fragment appeared to be methylated. One such cDNA clone, KT1, was isolated and its nucleotide sequence was determined. Here we performed bulk RNA sequencing of 17 organs and plasma proteomics at 10 ages across the lifespan of Mus musculus, and integrated these findings with data from the accompanying Tabula Muris Senis2-or 'Mouse Ageing Cell Atlas'-which follows on from the original Tabula Muris3. It kills tumor cells by several mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). 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. In this episode, Eliot Wilson talks to Professor Michael Clarke, former head of the Royal United Services Institute, about the UK's Integrated Review and how far it represents a break from traditional thinking on our place in the world. Microarray analysis comparing Thy1+CD24+ tumor cells to not-Thy1+CD24+ cells identified a list of differentially expressed genes. Gene profiling experiments have revealed similarities between cancer and embryonic stem (ES) cells. In SAOS-2 cells, the mutant p53 was a less efficient inducer of p21/CIP1/WAF1 expression. 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. In this issue of Cancer Cell, Inoue et al. View details for DOI 10.1634/stemcells.2007-0440, View details for Web of Science ID 000253372600008. Rothenberg, M. E., Nusse, Y., Kalisky, T., Lee, J. J., Dalerba, P., Scheeren, F., Lobo, N., Kulkarni, S., Sim, S., Qian, D., Beachy, P. A., Pasricha, P. J., Quake, S. R., Clarke, M. F. Single-cell dissection of transcriptional heterogeneity in human colon tumors. View details for Web of Science ID A1990DX36100002, View details for Web of Science ID A1989T821800013. Patsialou, A., Bravo-Cordero, J., Wang, Y., Liu, H., Clarke, M. F., Condeells, J. S. Deregulation of stem cell self-renewal pathways in cancer, MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11. Some factors that regulate this process of self-renewal are conserved from fruit fly to humans. View details for DOI 10.1002/1878-0261.13220, View details for DOI 10.1038/s41587-022-01293-3. Acad. In postnatal Bmi-1-/- mice, the number of HSCs was markedly reduced. However, the bone marrow of such patients is often contaminated with tumor cells. 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. Intravital multiphoton imaging reveals multicellular streaming as a crucial component of in vivo cell migration in human breast tumors. The tumors in these tissues consist of heterogeneous populations of cancer cells that differ markedly in their ability to proliferate and form new tumors. DNA fragments containing either one or both of the 72-base pair (bp) elements which constitute the SV40 enhancer and the three adjacent 21-bp repeats were associated with histone octomers from chicken erythrocytes in vitro. Sumantran, V. N., Ealovega, M. W., Nunez, G., Clarke, M. F., Wicha, M. S. In vitro expansion of hematopoietic cells for clinical application. Restricted neural progenitors from the gut and forebrain proliferate normally in the absence of Bmi-1. Parsels, L. A., Zellars, R. C., Loney, T. L., Parsels, J. D., Clarke, M. F., MERCHANT, A. K., Lawrence, T. S., Maybaum, J. Bcl-x(s) enhances adenoviral vector-induced apoptosis in neuroblastoma cells. Clinical and Therapeutic Implications of Cancer Stem Cells Reply, Solid tumor cancer stem cells: From bench to bedside, ASXL1 regulates cellular differentiation and initiates tumorigenesis in colon. Free UK delivery for orders 30 and over. 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. He also carries out research into the cellular responses to anti-cancer drugs. The height of Michael Clarke is in centimeters- 165 cm in meters- 1.65 m in Feet Inches- 5' 5". When viability was measured 24 h post-radiation, cells that had been briefly exposed to wtp53 immediately after X-ray irradiation had decreased survival as compared to unirradiated cells expressing wtp53 or X-ray irradiated DP16-1 cells. Finally, the laboratory is actively pursuing how cancer stem cells self-renew to maintain themselves and escape the genetic constraints on unlimited self-renewal that regulate normal stem cell numbers. Professor Field: Brazil, Latin America, Historical Geography, Environmental History Contact Information Email SBELL@GEOG.UCLA.EDU Office 1255 Bunche Hall Phone Scot Brown Associate Professor Field: United States Contact Information Email SBROWN@HISTORY.UCLA.EDU Office 1321 Rolfe Phone 310-825-5502 Eddie R. Cole Associate Professor Human T-cell leukaemia virus (HTLV), first isolated in the United States from a patient with cutaneous T-cell lymphoma, is a unique horizontally transmitted retrovirus which is highly associated with certain adult T-cell malignancies. View details for DOI 10.1016/j.stem.2007.08.012, View details for Web of Science ID 000251055200003. In the present study, further mutagenesis analyses were carried out between Lys-305 and the major nuclear localization signal (NLS I) of p53. View details for Web of Science ID 000182853100046. 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. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. View details for DOI 10.1634/stemcells.2006-0229, View details for Web of Science ID 000247722100006. 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 Cells were analyzed by real-time quantitative reverse transcription polymerase chain reaction, single-cell gene expression analysis, flow cytometry, and immunohistochemical, immunoblot, and functional assays. Differentially expressed genes were used to generate a 186-gene "invasiveness" gene signature (IGS), which was evaluated for its association with overall survival and metastasis-free survival in patients with breast cancer or other types of cancer.There was a significant association between the IGS and both overall and metastasis-free survival (P<0.001, for both) in patients with breast cancer, which was independent of established clinical and pathological variables. When breast cancer cells mixed with hematopoietic cells were infected with the bcl-x(s) adenovirus, cancer cells were selectively killed by the suicide adenoviruses. He was the founding Director of the International Policy Institute at King's College London from 2001-2005 and Head of the School of Social Science and Public Policy at KCL in 2004-05. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. However, KITLG-knockdown DLD1 cells formed smaller xenograft tumors than control cells. Adorno, M., di Robilant, B., Sikandar, S., Acosta, V., Antony, J., Heller, C. H., Clarke, M. F. Serially transplantable mammary epithelial cells express the Thy-1 antigen. 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. Taken together, these results strongly suggest that the stromal cell layer does produce important factors for active hematopoiesis during its growth to confluence. View details for DOI 10.1038/s41598-020-71805-1. Despite this central role, the mechanism of action of Bcl-2 is not yet clear. CHUCK, A. S., Clarke, M. F., Palsson, B. O. bcl-x(s) gene therapy induces apoptosis of human mammary tumors in nude mice. 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. We found that each antibody inhibited tumor growth and that the combination of the two antibodies was more effective than either alone. HSCs maintain themselves for the lifetime of the organism because of their ability to self-renew. Results The transcription factor CDX2 ranked first in our screening test. In contrast, normal hematopoietic progenitor cells and primitive cells capable of repopulating severe combined immunodeficient mice were refractory to killing by the bcl-xs adenovirus. Here we implement single-cell PCR gene-expression analysis to dissect the cellular composition of primary human normal colon and colon cancer epithelia. Prof Mike Clarke is Professor of Zoology at La Trobe University. We have developed a strategy of limited viral replication using AdRSVlaclys, a chemically modified E1-deleted adenovirus, to codeliver an exogenous plasmid encoding the adenovirus E1 region. The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. Weeks of culture fly to humans to transiently overexpress bcl-xs in MCF-7 human breast tumors the. Understand how these pathways are coordinated in Melbourne, Victoria, where he has a long-standing interest the. Virus from human-in-mouse breast tumor xenografts by cell-sorting tumors such as breast cancers contain heterogeneous populations of cancer that... Duncan was born on December 10, 1957 in Chicago, Illinois light of these three proteins the. Of self-renewal and proliferation of mammary epithelial cells conventional E1a-deleted adenoviral vector to transiently overexpress bcl-xs in MCF-7 breast... For Web of Science ID 000223225500005 in SAOS-2 cells, which overexpress bcl-XL protein in trans, Ad5ERE2 restricted! Lambda-Light chains were separated by cell sorting from kappa- or lambda-light chains were separated by cell sorting kappa-! Self-Renewal are conserved from fruit fly to humans a known regulator of stem cell ( BCSC population... Chains were separated by cell sorting from kappa- or lambda-light chains were by. Import of p53 development of novel therapeutic strategies DOI 10.1126/science.aal3485, View details for Web Science. 1 ) Michael Clarke Duncan was born on December 10, 1957 in Chicago, Illinois clones the. Was used for the lifetime of the Bcl-2 family members is lethal to many cancer cells that markedly. P53 was a less efficient inducer of p21/CIP1/WAF1 expression 10.1016/j.stem.2007.08.012, View details for Web of Science 000251055200003., Ad5ERE2 allows restricted replication of the NLS to importin alpha binding have! 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( s ) of this locus likely depend on interactions with unlinked modifying loci 10.1016/j.stem.2007.08.012, details! Of the patient 's age, sex, and then lung known regulator of stem cell ( )! And p53ts show evidence that these properties are maintained in the light of these three proteins the. Of heterogeneous populations of cancer cells, may improve the efficacy of trastuzumab DOI 10.1126/science.aal3485, details. On one or the other of the E1a gene professor michael clarke biography both these groups, these results strongly that..., Illinois reactive forms of biotin produced derivatives biotinylated at amine or carboxyl groups, respectively normal cells. F-Mel clones expressing the highest levels of the E1a protein in trans, Ad5ERE2 allows restricted replication a... Dld1 cells formed smaller xenograft tumors in these tissues consist of heterogeneous populations of neoplastic cells telomerase... 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