It has been reported that Lysine-305 is needed for the nuclear import of the p53 protein (Liang et al., 1998). In both breast cancers and central nervous system tumors, cancer cells differ in their ability to form tumors. 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. Parks, I. K., Klug, C. A., Li, K. J., Jerabek, L., Li, L. H., Nanamori, M., Neubig, R. R., Hood, L., Weissman, I. L., Clarke, M. F. A novel, conditionally replicative adenovirus for the treatment of breast cancer that allows controlled replication of E1a-deleted adenoviral vectors. Hernandez-Alcoceba, R., Pihalja, M., Wicha, M. S., Clarke, M. F. A bipartite nuclear localization signal is required for p53 nuclear import regulated by a carboxyl-terminal domain, Germ cell tumor: Differentiation of viable tumor, mature teratoma, and necrotic tissue with FDG PET and kinetic modeling. 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 . Additionally, we suggest that constitutive expression of c-myb does not block early commitment events such as activation of histone Hl', subsequent chromatin condensation, and alteration of proliferation-related gene expression. We then determined the effects of intratumoral injection of bcl-xs adenovirus on solid MCF-7 tumors in nude mice. All together, these findings link important stem cell regulators like Bmi1/Usp16 and Cdkn2a to Wnt signaling, and have implications for designing therapies for conditions, like DS, aging or degenerative diseases, where the Wnt pathway is hampered. War in Ukraine 2022: Prof. Michael Clarke analysis 116 videos 3,380 views Updated 5 days ago Defence and security analyst Professor Michael Clarke's observations mostly on Sky News. To enrich mRNAs predominantly expressed in uncommitted cell lineages, 54 000 cDNA clones generated from a highly enriched population of HSCs and a mixed population of stem and early multipotent progenitor (MPP) cells were arrayed on nylon membranes (macroarray or high-density array), and subtracted with cDNA probes derived from mature lineage cells including spleen, thymus, and bone marrow. Professor Clark is someone that should teach all students. 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. This development may play an important role in realizing human gene therapy. View details for DOI 10.1371/journal.pone.0002428, View details for Web of Science ID 000263280700013, View details for PubMedCentralID PMC2413402, View details for Web of Science ID 000454834700190. 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. However, attempts to develop stable long-term human bone marrow cultures have been unsuccessful. 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. 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. A., Jones, R. C., Nicolis di Robilant, B. n., Nong, R. Y., Norton, J. Thomas Jeffrey Hanks ( Concord, California; 9 de julio de 1956) es un actor y director de cine estadounidense. Two distinct technical approaches were used for most organs: one approach, microfluidic droplet-based 3'-end counting, enabled the survey of thousands of cells at relatively low coverage, whereas the other, full-length transcript analysis based on fluorescence-activated cell sorting, enabled the characterization of cell types with high sensitivity and coverage. 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. 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. A better understanding of the molecular mechanisms underlying metastasis is needed to develop more effective treatments. c-sis gene expression has been demonstrated in a variety of human tumors, although generally at levels much lower than those shown to transform cells in vitro. Il termine stato coniato dal giornalista statunitense Gary Wolf nel 2006. The tumorigenic subpopulation could be serially passaged: each time cells within this population generated new tumors containing additional CD44(+)CD24(-/low)Lineage(-) tumorigenic cells as well as the phenotypically diverse mixed populations of nontumorigenic cells present in the initial tumor. Lee, J. J., Rothenberg, M. E., Seeley, E. S., Zimdahl, B., Kawano, S., Lu, W., Shin, K., Sakata-Kato, T., Chen, J. K., Diehn, M., Clarke, M. F., Beachy, P. A. The Shep-1 neuroblastoma cell line is highly resistant to IR. Three well-known tumor suppressors, p53, p16INK4a, and p19ARF, have been connected to the limiting of stem cell self-renewal and proliferation. He also carries out research into the cellular responses to anti-cancer drugs. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. View details for DOI 10.1038/s41587-021-01188-9, View details for DOI 10.7554/eLife.70692.sa2, View details for Web of Science ID 000715795700001, View details for Web of Science ID 000680263504041, View details for DOI 10.1200/JCO.2021.39.15_suppl.e15067, View details for Web of Science ID 000708120301134, View details for DOI 10.1200/JCO.2021.39.15_suppl.3105, View details for Web of Science ID 000708120601279. View details for DOI 10.1073/pnas.1006732107, View details for Web of Science ID 000283184800050, View details for PubMedCentralID PMC2964232. At present, neither the role that the stromal cell extra-cellular matrix (ECM) plays in influencing stroma behavior is well understood nor are the effects of stroma aging. Bcl-XS overexpressed in MCF-7 cells by stable transfection does not affect viability by itself but induces a marked increase in chemosensitivity to VP-16 or taxol. View details for Web of Science ID A1993KD78500072. View details for Web of Science ID A1984SP90200011. RADIATION THERAPY ONCOLOGY GROUP TRANSLATIONAL RESEARCH PROGRAM STEM CELL SYMPOSIUM: INCORPORATING STEM CELL HYPOTHESES INTO CLINICAL TRIALS. Recent studies have uncovered a number of Bcl-2-related gene products that regulate apoptosis either negatively or positively, and Bcl-2 forms heterodimers with at least one of these proteins, Bax. We were able to distinguish the tumorigenic (tumor initiating) from the nontumorigenic cancer cells based on cell surface marker expression. 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. in Management and an M.S. In contrast, at least some of these sites were not methylated in DNA from the B-cells expressing high levels of DR alpha mRNA. Olivieri, J., Dehghannasiri, R., Wang, P. L., Jang, S., de Morree, A., Tan, S. Y., Ming, J., Wu, A., Consortium, T., Quake, S. R., Krasnow, M. A., Salzman, J. TACH101, a first-in-class pan inhibitor of KDM4 histone lysine demethylases. We have examined the respiratory burst and arachidonic acid oxygenation that accompany phagocytosis in macrophages. Professor of Health in Social Science; College Dean International; EFI Director of Global Communities. The height of Michael Clarke is in centimeters- 165 cm in meters- 1.65 m in Feet Inches- 5' 5". View details for DOI 10.1073/pnas.0530291100, View details for Web of Science ID 000182058400082, View details for PubMedCentralID PMC153034. View details for Web of Science ID 000076744000010. (2007) analyze the relationship between CSC and tumor metastasis. Although cancer cell lines provide invaluable information, their biological properties often differ in crucial ways from de novo cancer cells. Temporary expression of wild-type p53 activity in the absence of drug treatment caused some loss of clonogenicity, although the magnitude of this cytotoxic effect was small compared with the level of cell kill obtained by treatment with cytotoxic drugs for similar periods of time, indicating that HT29 cells are not highly sensitive to induction of programmed cell death by wild-type p53. The mammary epithelium undergoes several rounds of extensive proliferation during the female reproductive cycle. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. View details for Web of Science ID 000186360800006. View details for Web of Science ID 000255592400041, View details for Web of Science ID 000246136200023. View details for Web of Science ID 000168861600008. To characterize further the function of these two domains, we demonstrate in this report that the previously described major nuclear localization signal works together with Lys(305)-Arg(306) to form a bipartite and functional nuclear localization sequence (NLS) for p53 nuclear import. Michael Clarke, MD is a Professor of Medicine at Stanford University. While the class is nonetheless challenging, Professor Clark does his best to help all students pass. Join Facebook to connect with Michael Clarke and others you may know. 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. Patients generally die of cancer after the failure of current therapies to eliminate residual disease. Thus, loss of expression of the alpha-catenin tumor suppressor in hematopoietic stem cells may provide a growth advantage that contributes to human MDS or AML with del(5q). We report that Bcl-XL, which functions like Bcl-2 to inhibit apoptosis, is highly expressed in MCF-7 human breast carcinoma cells. Therefore, infection with this virus preferentially kills estrogen receptor-positive breast cancer cells, or cells growing under hypoxic conditions. Street. View details for Web of Science ID A1988L925300043. The complexity and inefficiency of chromatin immunoprecipitation strategies restrict their sensitivity and application when examining rare cell populations. In a pooled database of all patient cohorts, the rate of 5-year disease-free survival was higher among 23 patients with stage II CDX2-negative tumors who were treated with adjuvant chemotherapy than among 25 who were not treated with adjuvant chemotherapy (91% vs. 56%, P=0.006). In this study we describe the effect on murine erythroleukemia cells, transfected with a temperature-sensitive mutant p53, of exposure to the differentiating agent dimethylsulfoxide (DMSO). These experiments demonstrate the feasibility of using bcl-xs gene therapy to induce apoptosis in human breast tumors. We screened for genetic polymorphisms that were linked to differences between mouse strains in the numbers of long-term reconstituting HSCs or restricted progenitors in the bone marrow. These data support a model in which low levels of sis gene expression in tumors contribute to the acquisition of some features of transformation but require complementation by other genes or factors to produce a fully malignant phenotype. He is so driven about his work and is so charismatic to his students. View details for DOI 10.1158/0008-5472.CAN-06-2030, View details for Web of Science ID 000244137300026. View details for DOI 10.1056/NEJMoa1506597, View details for Web of Science ID 000368404800006, View details for PubMedCentralID PMC4784450. Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy. U.S.A. 1995;92:11024-11028) is used in combination with Ad5ERE2, the ability of both viruses to induce cell death is dramatically increased, and the effect can be modulated by addition of the antiestrogen tamoxifen. In this report, we analyzed the possible existence of cis-acting sequences involved in intracellular trafficking of the p53 protein. 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