Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. When combined with the prognostic criteria of the National Institutes of Health, the IGS was used to stratify patients with high-risk early breast cancer into prognostic categories (good or poor); among patients with a good prognosis, the 10-year rate of metastasis-free survival was 81%, and among those with a poor prognosis, it was 57%. 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. We collected eleven pancreatic tumors and identified three shared and five private neoplastic cell populations, offering insight into the origins of neuroendocrine and exocrine tumors. Cytoplasmic sequestration of the p53 tumor suppresser protein has been proposed as a mechanism involved in abolishing p53 function. Dylla, S. J., Beviglia, L., Park, I., Chartier, C., Raval, J., Ngan, L., Pickell, K., Aguilar, J., Lazetic, S., Smith-Berdan, S., Clarke, M. F., Hoey, T., Lewicki, J., Gurney, A. L. Characterizing metastatic cancer stem cells from human breast cancer. 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. A., Spallino, E., Aaron, K. A., Concepcion, W., Gardner, J. M., Kelly, B., Neidlinger, N., Wang, Z., Crasta, S., Kolluru, S., Morri, M., Tan, S. Y., Travaglini, K. J., Xu, C., Alcantara-Hernandez, M., Almanzar, N., Antony, J., Beyersdorf, B., Burhan, D., Calcuttawala, K., Carter, M. M., Chan, C. K., Chang, C. A., Chang, S., Colville, A., Culver, R. N., Cvijovic, I., D'Amato, G., Ezran, C., Galdos, F. X., Gillich, A., Goodyer, W. R., Hang, Y., Hayashi, A., Houshdaran, S., Huang, X., Irwin, J. C., Jang, S., Juanico, J. V., Kershner, A. M., Kim, S., Kiss, B., Kong, W., Kumar, M. E., Kuo, A. H., Leylek, R., Li, B., Loeb, G. B., Lu, W., Mantri, S., Markovic, M., McAlpine, P. L., de Morree, A., Mrouj, K., Mukherjee, S., Muser, T., Neuhofer, P., Nguyen, T. D., Perez, K., Phansalkar, R., Puluca, N., Qi, Z., Rao, P., Raquer-McKay, H., Schaum, N., Scott, B., Seddighzadeh, B., Segal, J., Sen, S., Sikandar, S., Spencer, S. P., Steffes, L., Subramaniam, V. R., Swarup, A., Swift, M., Van Treuren, W., Trimm, E., Veizades, S., Vijayakumar, S., Vo, K. C., Vorperian, S. K., Wang, W., Weinstein, H. N., Winkler, J., Wu, T. T., Xie, J., Yung, A. R., Zhang, Y., Detweiler, A. M., Mekonen, H., Neff, N. F., Sit, R. V., Tan, M., Yan, J., Bean, G. R., Charu, V., Forgo, E., Martin, B. 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. Usp16 contributes to somatic stem-cell defects in Down's syndrome. View details for DOI 10.1073/pnas.1212188109, View details for Web of Science ID 000312605600104, View details for PubMedCentralID PMC3528539. View details for Web of Science ID A1995TE58500016. Gene expression analysis of cells isolated from nonadherent mammospheres revealed overlapping genetic programs with other stem and progenitor cells and identified new markers that may be useful in the identification of mammary stem cells. Using mammary epithelial-specific mouse models targeting Trp53 and Cdkn2a, the gene coding for p16INK4a and p19ARF, we demonstrate that p53, p16INK4a, and p19ARF do not play a significant role in the limitation of normal mammary epithelium self-renewal and proliferation, whereas in the presence of the inflammatory cytokine TNF-, Trp53-/-Cdkn2a-/- mammary basal cells exhibit amplified proliferation. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Xenograft tumors were grown from control and KIT-knockdown DLD1 and UM-COLON#8 cells in immunocompromised mice and compared. 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. Single-cell RNA sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. These results indicate that the CSD can regulate p53 nuclear import by controlling access of the NLS to importin alpha binding. The regulation of hematopoietic stem cell (HSC) homeostasis is not well understood. Comparing the expression signature of normal HSC to that of LSC, we identified 3,005 differentially expressed genes. 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. KrasG12D -independent tumor cells show a strong mesenchymal profile with active RAS-RAF-MEK-ERK (MAPK/ERK) signaling. View details for DOI 10.1056/NEJMoa1506597, View details for Web of Science ID 000368404800006, View details for PubMedCentralID PMC4784450. Zabala, M., Lobo, N. A., Seoane, J. To determine the role of these proteins in maintaining cancer cell viability, an adenovirus vector that expresses bcl-xs, a functional inhibitor of these proteins, was constructed. Sufficient new cells have to be produced to maintain the integrity of a tissue, but excessive proliferation resulting in tumorigenesis needs to be prevented. View details for Web of Science ID 000075125200067. We investigated the role of the RTK KIT in development of human colon cancer.An array of 137 patient-derived colon tumors and their associated xenografts were analyzed by immunohistochemistry to measure levels of KIT and its ligand KITLG. View details for DOI 10.1016/j.stem.2016.11.007, View details for PubMedCentralID PMC5341693. View details for DOI 10.1186/s13058-018-1006-y, View details for Web of Science ID 000447203300001, View details for Web of Science ID 000440602000145, View details for Web of Science ID 000440602000051, View details for DOI 10.1200/JCO.2018.36.4_suppl.683, View details for Web of Science ID 000436174100659. Solid tumors such as breast cancers contain heterogeneous populations of neoplastic cells. 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. Finally, we show how gene expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to the ageing of the systemic circulation. Evidence from studies in murine and human embryonic stem cells indicates that Polycomb group proteins play a dynamic role in concert with master transcriptional regulators in actively maintaining an undifferentiated state, suggesting that this mechanism applies to multiple types of stem cell. View details for DOI 10.1073/pnas.1121623109, View details for DOI 10.1158/1538-7445.AM2012-3331, View details for Web of Science ID 000209701505088, View details for DOI 10.1158/1538-7445.AM2012-1012, View details for Web of Science ID 000209701505194. Thus, Bmi-1 dependence distinguishes stem cell self-renewal from restricted progenitor proliferation in these tissues. p16Ink4a deficiency partially reverses the self-renewal defect in Bmi-1-/- neural stem cells. (2010) dissect the gene expression signature of ES cells into three functional modules and find that the Myc module, including genes targeted by Myc-interacting proteins, accounts for most of the similarity between ES and cancer cells. This will allow the characterization of crucial signaling pathways involved in processes such as self-renewal that are critical for tumor formation by the cancer cells within de novo tumors. Furthermore, we identify unique, CSC-specific, remodeling events. These data demonstrate that the transcomplementation of replication-deficient adenovirus with exogenous E1 DNA leads to limited replication, and this controlled replication enhances gene transfer efficiency of adenovirus in vivo. Analysis of HL-60 cells, a myeloid leukemia line with deletion of the 5q31 region, showed that the CTNNA1 promoter of the retained allele is suppressed by both methylation and histone deacetylation. Clarke, M. F., Gelmann, E. P., Reitz, M. S. RELATION OF RESPIRATORY BURST AND ARACHIDONATE METABOLISM DURING PHAGOCYTOSIS BY GUINEA-PIG ALVEOLAR MACROPHAGES. HSCs maintain themselves for the lifetime of the organism because of their ability to self-renew. http://med.stanford.edu/profiles/, Position:Assoc Director, Stanford Institute for Stem Cell & Regenerative Medicine, Biopsy of Human Tumors for Cancer Stem Cell Characterization: a Feasibility Study. 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. To evaluate the feasibility of positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) in patients with germ cell tumor (GCT) to monitor treatment and differentiate residual masses after chemotherapy.Twenty-six FDG PET studies were performed in 21 patients with GCT, FDG uptake of tumors was interpreted visually, and the lean standardized uptake value (SUVlean) was determined. The aim of the present study was to determine the effects of Bcl-xS expression on the viability of NB cells. The main objectives of his laboratory are to pursue how perturbations in the self-renewal machinery contribute to human diseases and to use the findings to aid the development of more effective treatment therapies.His laboratory has a long history of innovative findings which include: the first to demonstrate that inappropriate expression of a normal gene could cause a tumor; the first to identify a dominant-negative splice variant of an oncogene; the first to identify a molecular regulator of stem cell self-renewal; the first to identify a solid tumor stem cell (in breast cancer) and the first to demonstrate a molecular linkage of a self-renewal program used by normal mammary stem cells and breast cancer cells. 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. Human tumors where evidence of cancer stem cells has been published include tumors of the breast, brain, pancreas, head and neck, and colon. This study demonstrates that combining global gene expression analysis with detailed annotated pathway resources applied to highly enriched normal and malignant stem cell populations, can yield an understanding of the critical pathways regulating cancer stem cells. Adjunct Senior Lecturer Dr Urs Wermuth. Imatinib inhibited growth of KIT(+) colon cancer organoids in culture and growth of xenograft tumors in mice. 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. This sequential antibody strategy, combining a tumor-targeting antibody with a second antibody that activates the host innate immune system, may improve the therapeutic effects of antibodies against breast cancer and other HER2-expressing tumors. We report here that the genes for HLA class I antigens are also highly methylated in the T-ALL T-cell lines relative to the same genes in the ATL T-cell lines, normal peripheral blood T cells, and autologous normal B-cell lines. View details for Web of Science ID A1991EY27300001. 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. The Polycomb protein Bmi1 is absolutely required for the maintenance of both adult HSCs and neural stem cells. Michael Clarke (academic) is a British academic who specialises in defence studies. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. 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. In recent years solid tumors were studied utilizing similar techniques in mice. Therefore, to better treat cancer it may be necessary to develop novel methods to overcome the effects of the Bcl-2 family. Deletion of MYD88 or TLR2 in the intestinal epithelium markedly reduces DSS-induced colitis regeneration and spontaneous tumour development in mice. Tom Hanks. 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. He has also acted as a reviewer for the EPSRC and for funding councils in Austria, Finland, France and Germany. 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. 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. Understanding and reproducing the molecular interactions between bone marrow stromal cells and stem cells in tissue culture models is therefore the critical step in successful bone marrow tissue culture. Recent studies have begun to elucidate the mechanisms controlling hematopoietic stem cell (HSC) self-renewal. To achieve long-lasting responses in the clinic to RAS-fueled cancer, treatment will need to focus in parallel on obstructing tumors from adapting to oncogene inhibition. 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. 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). 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. 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