Solid CRC tissues, either primary tissues collected from surgical specimens or xenografts established in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, were disaggregated into single-cell suspensions and analyzed by flow cytometry. We examined the effect of lower levels of c-sis expression on the phenotype of NIH 3T3 fibroblasts. From August 1990 to June 1998, 29 males (25 NSGCT) were treated. 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. Bmi-1 was expressed at its highest levels in undifferentiated leukemia cells. We show that a set of active constituent enhancers, located within the two CD47 SEs, regulate CD47 expression in different cancer cell types and that disruption of CD47 SEs reduces CD47 gene expression. A spacer between this basic domain and NLS I is necessary for the entrance of p53 into the cell nucleus. He has a long-standing interest in the impact of fire upon fauna. Hoey, T., Yen, W., Axelrod, F., Basi, J., Donigian, L., Dylla, S., Fitch-Bruhns, M., Lazetic, S., Park, I., Sato, A., Satyal, S., Wang, X., Clarke, M. F., Lewicki, J., Gurney, A. Conclusions Lack of CDX2 expression identified a subgroup of patients with high-risk stage II colon cancer who appeared to benefit from adjuvant chemotherapy. 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. Here we show that the short half-lives of retroviruses limit the distance that they can effectively travel in solution by Brownian motion, and thus the possibility of successful gene transfer. It is most highly expressed in bone marrow followed by fetal liver, spleen, and then lung. Replication-deficient viral vectors are currently being used in gene transfer strategies to treat cancer cells. The N-bGM-CSFs demonstrated GM-CSF receptor specific binding that was displaceable by excess underivatized protein, with the detected fluorescence signal decreasing with increasing biotin to protein molar ratio. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. The data are consistent with formation of a core particle on one or the other of the repeated enhancer sequences. 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. Many cancers overexpress a member of the bcl-2 family of inhibitors of apoptosis. Restoration of CTNNA1 expression in HL-60 cells resulted in reduced proliferation and apoptotic cell death. 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. As precision medicine increases the response rate of treatment, tumors frequently bypass inhibition and reoccur. Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy. 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. Epithelial-to-mesenchymal transition has been shown to correlate with therapy resistance, but the functional link and signalling pathways remain to be elucidated. Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Enforced expression of miR-142 or miR-150 in normal mouse mammary stem cells resulted in the regeneration of hyperproliferative mammary glands in vivo. 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. Single cell transcriptomics is revolutionising our understanding of tissue and disease heterogeneity, yet cell type identification remains a partially manual task. Solid tumors arise in organs that contain stem cell populations. Investigating mechanisms of cancer stern cell radioresistance. 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 In contrast, BMP7, a NODAL antagonist with context-dependent functions, is produced by basal cells and restrains progenitor cell proliferation. Orhan Eren Akgun. Dr. Jim Clarke is an Adjunct Professor of Civil and Environmental Engineering and an Adjunct Professor of Earth and Environmental Sciences at Vanderbilt University. This raises the issue of whether there is a conserved mechanism to effect self-renewing divisions. Here, we report a mouse model that, in the absence of p53 and the presence of oncogenic KrasG12D , develops breast tumors. These chemically reactive forms of biotin produced derivatives biotinylated at amine or carboxyl groups, respectively. Of five long-term NSGCT survivors, four were treated in first relapse with platinum-sensitive disease. His writingson justice, ethics, democracy, and markets--have been translated into 27 languages. A., Beachy, P. A., Berdnik, D., Bilen, B., Brownfield, D., Cain, C., Chan, C. K., Chen, M. B., Clarke, M. F., Conley, S. D., Demers, A., Demir, K., de Morree, A., Divita, T., du Bois, H., Ebadi, H., Espinoza, F. H., Fish, M., Gan, Q., George, B. M., Gillich, A., Gomez-Sjoberg, R., Green, F., Genetiano, G., Gu, X., Gulati, G. S., Hahn, O., Haney, M. S., Hang, Y., Harris, L., He, M., Hosseinzadeh, S., Huang, A., Huang, K. C., Iram, T., Isobe, T., Ives, F., Jones, R. C., Kao, K. S., Karnam, G., Kershner, A. M., Khoury, N., Kim, S. K., Kiss, B. M., Kong, W., Krasnow, M. A., Kumar, M. E., Kuo, C. S., Lam, J., Lee, D. P., Lee, S. E., Lehallier, B., Leventhal, O., Li, G., Li, Q., Liu, L., Lo, A., Lu, W., Lugo-Fagundo, M. F., Manjunath, A., May, A. P., Maynard, A., McKay, M., McNerney, M. W., Merrill, B., Metzger, R. J., Mignardi, M., Min, D., Nabhan, A. N., Ng, K. M., Nguyen, P. K., Noh, J., Nusse, R., Patkar, R., Peng, W. C., Penland, L., Pollard, K., Puccinelli, R., Qi, Z., Rando, T. A., Rulifson, E. J., Segal, J. M., Sikandar, S. S., Sinha, R., Sit, R. V., Sonnenburg, J., Staehli, D., Szade, K., Tan, M., Tato, C., Tellez, K., Torrez Dulgeroff, L. B., Travaglini, K. J., Tropini, C., Tsui, M., Waldburger, L., Wang, B. M., van Weele, L. J., Weinberg, K., Weissman, I. L., Wosczyna, M. N., Wu, S. M., Xiang, J., Xue, S., Yamauchi, K. A., Yang, A. C., Yerra, L. P., Youngyunpipatkul, J., Yu, B., Zanini, F., Zardeneta, M. E., Zee, A., Zhao, C., Zhang, F., Zhang, H., Zhang, M. J., Zhou, L., Zou, J. Scheeren, F. A., Kuo, A. H., van Weele, L. J., Cai, S., Glykofridis, I., Sikandar, S. S., Zabala, M., Qian, D., Lam, J. S., Johnston, D., Volkmer, J. P., Sahoo, D., van de Rijn, M., Dirbas, F. M., Somlo, G., Kalisky, T., Rothenberg, M. E., Quake, S. R., Clarke, M. F. A cell-intrinsic role for TLR2 MYD88 in intestinal and breast epithelia and oncogenesis. Hernandez-Alcoceba, R., Pihalja, M., Nunez, G., Clarke, M. F. Molecular cloning and characterization of a novel regulator of G-protein signaling from mouse hematopoietic stem cells. We used Bcl-XS, a dominant negative inhibitor of Bcl-2 and Bcl-XL, to demonstrate the role of these genes in modulating chemotherapy-induced apoptosis. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance. The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival. Yoo, S., Chandhasin, C., Del Rosario, J., Chen, Y. K., Stafford, J., Perabo, F., Clarke, M. F. Inhibition of histone lysine demethylases with TACH101, a first-in-class pan-inhibitor of KDM4. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. A., Sim, S., Okamoto, J., Johnston, D. M., Qian, D., Zabala, M., Bueno, J., Neff, N. F., Wang, J., Shelton, A. To explore the possible role of c-sis expression in HTLV-induced disease, we have obtained cDNA clones of c-sis from HUT-102 cells. Furthermore, the oxygenation of arachidonic acid requires little of the oxygen consumed by phagocytosing alveolar macrophages. Hisamori, S., Dalerba, P., Shimono, Y., Rothenberg, M. E., Zabara, M., Cai, S., Qian, D., Clarke, M. F. Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer. 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. Furthermore, the tumorigenic CD44(+) cells differentially express the BMI1 gene, at both the RNA and protein levels. View details for Web of Science ID 000243488100004. [1] During the 2022 Russian invasion of Ukraine, he served as Sky News ' security and defence analyst. The possible significance of this finding is discussed. When applied to diverse tissue types and organisms, CytoTRACE outperformed previous methods and nearly 19,000 annotated gene sets for resolving 52 experimentally determined developmental trajectories. In contrast to wild-type MEL cells, both clones failed to display phenotypic markers of differentiation and continued to proliferate for up to 10 days of culture. Herein, we present a discussion around the issues facing treatment of patients with CRCliver metastases, including the relationship of discretegene signatures with prognosis. Parashurama, N., Lobo, N. A., Ito, K., Mosley, A. R., Habte, F. G., Zabala, M., Smith, B. R., Lam, J., Weissman, I. L., Clarke, M. F., Gambhir, S. S. Effect of stimulation of natural killer cells with an anti-CD137 mAb on the efficacy of trastuzumab, cetuximab, and rituximab. However, multipotent progenitors lack the ability to self-renew, therefore their mitotic capacity and expansion potential are limited and they are destined to eventually stop proliferating after a finite number of cell divisions. Disruption of the regulation of self-renewal results in cancer. Zarour, L. R., Anand, S., Billingsley, K. G., Bisson, W. H., Cercek, A., Clarke, M. F., Coussens, L. M., Gast, C. E., Geltzeiler, C. B., Hansen, L., Kelley, K. A., Lopez, C. D., Rana, S. R., Ruhl, R., Tsikitis, V. L., Vaccaro, G. M., Wong, M. H., Mayo, S. C. Role of epithelial to mesenchymal transition associated genes in mammary gland regeneration and breast tumorigenesis. Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. Reply. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. The efficiency of gene therapy strategies against cancer is limited by the poor distribution of the vectors in the malignant tissues. Although wild-type p53 is expressed in virtually all neuroblastoma tumors, treatment failures secondary to inadequate local control with radiotherapy are a problem in patients with advanced stage disease. Current page 1; Page 2; While the class is nonetheless challenging, Professor Clark does his best to help all students pass. Inhibiting USP16 rescues stem cell aging and memory in an Alzheimer's model. Vorperian, S. K., Moufarrej, M. N., Tabula Sapiens Consortium, Quake, S. R., Jones, R. C., Karkanias, J., Krasnow, M., Pisco, A. O., Quake, S. R., Salzman, J., Yosef, N., Bulthaup, B., Brown, P., Harper, W., Hemenez, M., Ponnusamy, R., Salehi, A., Sanagavarapu, B. We extend this concept to identify cell types of origin using the Tabula Sapiens transcriptomic cell atlas as well as individual tissue transcriptomic cell atlases in combination with the Human Protein Atlas RNA consensus dataset. 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. 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. Chandhasin, C., Yoo, S., Del Rosario, J., Chen, Y. K., Stafford, J., Perabo, F., Clarke, M. F. Depletion of Trp53 and Cdkn2a Does Not Promote Self-Renewal in the Mammary Gland but Amplifies Proliferation Induced by TNF-. In addition to his clinical duties in the division of Oncology, Dr. Clarke maintains a laboratory focused on two areas of research: i) the control of self-renewal of normal stem cells and their malignant counterparts; and ii) the identification and characterization of cancer stem cells. The DR alpha genes in both cell lines are hypermethylated relative to the same genes in T-cell lines infected with human T-cell leukemia virus (HTLV) and derived from patients with adult T-cell leukemia/lymphoma (ATL). In order for treatment to be effective long term, the mechanisms enabling treatment adaptation need to be understood. 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. 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. T-All ) express HLA-DR antigens, whereas the isogenic T-cells do not to... Of normal stem cells is most highly expressed in bone marrow followed by fetal liver spleen! And defence analyst reactive forms of biotin produced derivatives biotinylated at amine or groups. 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