These studies show that the human retrovirus HTLV, which has been demonstrated to be associated with certain T cell malignancies, can infect B cells or B cell precursors. View details for Web of Science ID 000316614600063. However, the consequences of the underlying gene-dosage imbalance on adult tissues remain poorly understood. When organoids were depleted of cKit(+) cells using a toxin-conjugated antibody, organoid formation decreased.cKit marks small intestinal Paneth cells and a subset of colonic goblet cells that are regulated by Notch signaling and support Lgr5(+) stem cells. 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. These results validate the stem cell working model in human CRC and provide a highly robust surface marker profile for CRC stem cell isolation. This study thus establishes a key RNA-based feature of developmental potential and a platform for delineation of cellular hierarchies. 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. View details for DOI 10.1053/j.gastro.2015.05.042, View details for Web of Science ID 000360269800039, View details for PubMedCentralID PMC4550533. 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. Differences in self-renewal pathways between normal and malignant stem cells could be targeted by new therapeutic agents to eliminate cancer stem cells. These breast tumors are comprised of phenotypically diverse populations of breast cancer 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. The tumorigenic cells displayed stem cell-like properties in that they were capable of generating new tumors containing additional stem cells as well as regenerating the phenotypically mixed populations of non-tumorigenic cells present in the original tumor. Epigenetic regulation of normal and cancer stem cells, Neurobiology: At the root of brain cancer, Chronic myelogenous leukemia - Identifying the hydra's heads, Therapeutic implications of cancer stem cells. This is an overview of the elements and molecules involved in p53 nucleocytoplasmic transportation. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. Together, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Identification of a novel microRNA-mediated pathway that regulates chemoresistance in breast cancer will facilitate the development of novel therapeutic strategies. Discover Michael Clarke 's Biography, Age, Height, Physical Stats, Dating/Affairs, Family and career updates. Ayash, L. J., Clarke, M., Silver, S. M., Braun, T., Uberti, J., Ratanatharathorn, V., Reynolds, C., Ferrara, J., Broun, E. R., Adams, P. T. Evaluation of a new dual-specificity promoter for selective induction of apoptosis in breast cancer cells. In several forms of human cancer, only a phenotypic subset of cancer cells, usually termed "cancer stem cells" (CSC), can initiate tumor growth when transplanted. We discuss possible functional consequences of such nucleosome positioning. Anaesthesia 2001, 56(5), 486-487. EW replicates in IEC subsets differing in their basal type I IFN transcription and induces IRF3-dependent and IRF3-augmented transcription, but not NF-B-dependent or type I IFN transcripts. View details for DOI 10.1126/science.aax0249. 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. Diehn, M., Cho, R. W., Ailles, L., Lam, J. S., Kaplan, M. J., Somlo, G., Weissman, I. L., Clarke, M. F. Implications of Cancer Stem Cells for Tumor Metastasis. Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J., Clarke, M. F. Mesenchymal tumor cells drive adaptive resistance of Trp53-/- breast tumor cells to inactivated mutant Kras. Some mice were given the RTK inhibitor imatinib after injection of cancer cells; tumor growth was measured based on bioluminescence. 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. This genetic signature of tumorigenic breast-cancer cells was even more strongly associated with clinical outcomes when combined with the WR signature in breast cancer. View details for Web of Science ID 000075125200067. Using model cell lines (NIH-3T3 and CV-1), it was shown that gene transfer rates can be increased by more than an order of magnitude using the same concentration infection medium. 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. The miR-30c-VIM/TWF1 signaling cascade is also associated with clinical outcome in breast cancer patients. Dalerba, P., Kalisky, T., Sahoo, D., Rajendran, P. S., Rothenberg, M. E., Leyrat, A. Thus a limiting serum component is responsible for the altered metabolic and growth rates. 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. Control experiments show that positioning is not due to the 21-bp repeats or to end effects. In this report, we have used intravital multiphoton microscopy to visualize the different migration patterns of human breast tumor cells in live primary tumors. We have studied the ability of c-myc and bcl-2 oncogenes to modulate p53 function. Other pathways have not been previously implicated in the regulation of cancer stem cell functions, including Ribosome and T Cell Receptor Signaling pathway. It is most highly expressed in bone marrow followed by fetal liver, spleen, and then lung. We examined such heterogeneity in the small intestine during rotavirus (RV) infection. 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. Ealovega, M. W., McGinnis, P. K., Sumantran, V. N., Clarke, M. F., Wicha, M. S. A RECOMBINANT BCL-X(S) ADENOVIRUS SELECTIVELY INDUCES APOPTOSIS IN CANCER-CELLS BUT NOT IN NORMAL BONE-MARROW CELLS. View details for DOI 10.1016/j.stem.2016.11.007, View details for PubMedCentralID PMC5341693. The lack of expression correlates with a lack of detectable HLA-DR mRNA. We have examined the respiratory burst and arachidonic acid oxygenation that accompany phagocytosis in macrophages. At a meeting of the Translation Research Program of the Radiation Therapy Oncology Group held in early 2008, attendees focused on updating the current state of knowledge in cancer stem cell research and discussing ways in which this knowledge can be translated into clinical use across all disease sites. In addition, dysregulation of stem cell self-renewal is a likely requirement for the development of cancer. We have previously investigated the expression of Bcl-x in neuroblastoma (NB) cell lines and have shown that Bcl-xL is expressed and functions to inhibit chemotherapy-induced apoptosis. 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. List A-Z. Disclosure of potential conflicts of interest is found at the end of this article. 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. Two cDNA clones of the human c-myb gene have been isolated from a CCRF-CEM leukemia cell cDNA library and sequenced in their entirety. We studied the effect of the combination of rapid culture medium exchange with the addition of the human hematopoietic growth factors interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin (Epo) on the proliferation and differentiation of human long-term bone marrow cultures (LTBMCs). Clarke, M. F., Fitzgerald, P. C., Brubaker, J. M., Simpson, R. T. DNA METHYLATION AND EXPRESSION OF HLA-DR-ALPHA. Thus, the development of proper sampling techniques or improved stem cell retention may be critical to obtain successful long-term cultures. In the absence of Bmi-1, the cyclin-dependent kinase inhibitor gene p16Ink4a is upregulated in neural stem cells, reducing the rate of proliferation. One such cDNA clone, KT1, was isolated and its nucleotide sequence was determined. View details for DOI 10.1038/s41586-020-2499-y. During dimethylsulfoxide (DMSO)-induced differentiation of Friend mouse erythroleukemia (MEL) cells there is a biphasic fall in c-myb mRNA levels. 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. 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. Only those cells within a tumor that have these two properties are called cancer stem cells. 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