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  • 1
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 49 ( 2017-12-05), p. 12994-12999
    Abstract: IL-22 has been identified as a cancer-promoting cytokine that is secreted by infiltrating immune cells in several cancer models. We hypothesized that IL-22 regulation would occur at the interface between cancer cells and immune cells. Breast and lung cancer cells of murine and human origin induced IL-22 production from memory CD4 + T cells. In the present study, we found that IL-22 production in humans is dependent on activation of the NLRP3 inflammasome with the subsequent release of IL-1β from both myeloid and T cells. IL-1 receptor signaling via the transcription factors AhR and RORγt in T cells was necessary and sufficient for IL-22 production. In these settings, IL-1 induced IL-22 production from a mixed T helper cell population comprised of Th1, Th17, and Th22 cells, which was abrogated by the addition of anakinra. We confirmed these findings in vitro and in vivo in two murine tumor models, in primary human breast and lung cancer cells, and in deposited expression data. Relevant to ongoing clinical trials in breast cancer, we demonstrate here that the IL-1 receptor antagonist anakinra abrogates IL-22 production and reduces tumor growth in a murine breast cancer model. Thus, we describe here a previously unrecognized mechanism by which cancer cells induce IL-22 production from memory CD4 + T cells via activation of the NLRP3 inflammasome and the release of IL-1β to promote tumor growth. These findings may provide the basis for therapeutic interventions that affect IL-22 production by targeting IL-1 activity.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2017
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  • 2
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2009
    In:  Proceedings of the National Academy of Sciences Vol. 106, No. 15 ( 2009-04-14), p. 6309-6314
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 106, No. 15 ( 2009-04-14), p. 6309-6314
    Abstract: Notch and Wnt signals play essential roles in intestinal development and homeostasis, yet how they integrate their action to affect intestinal morphogenesis is not understood. We examined the interplay between these two signaling pathways in vivo, by modulating Notch activity in mice carrying either a loss- or a gain-of-function mutation of Wnt signaling. We find that the dramatic proliferative effect that Notch signals have on early intestinal precursors requires normal Wnt signaling, whereas its influence on intestinal differentiation appears independent of Wnt. Analogous experiments in Drosophila demonstrate that the synergistic effects of Notch and Wnt are valid across species. We also demonstrate a striking synergy between Notch and Wnt signals that results in inducing the formation of intestinal adenomas, particularly in the colon, a region rarely affected in available mouse tumor models, but the primary target organ in human patients. These studies thus reveal a previously unknown oncogenic potential of Notch signaling in colorectal tumorigenesis that, significantly, is supported by the analysis of human tumors. Importantly, our experimental evidence raises the possibility that Notch activation might be an essential initial event triggering colorectal cancer.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2009
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    detail.hit.zdb_id: 1461794-8
    SSG: 11
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    Location Call Number Limitation Availability
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  • 3
    In: Nature, Springer Science and Business Media LLC, Vol. 594, No. 7862 ( 2021-06-10), p. 265-270
    Abstract: Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine 1,2 . Patients with leukaemia can be identified using machine learning on the basis of their blood transcriptomes 3 . However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation 4,5 . Here, to facilitate the integration of any medical data from any data owner worldwide without violating privacy laws, we introduce Swarm Learning—a decentralized machine-learning approach that unites edge computing, blockchain-based peer-to-peer networking and coordination while maintaining confidentiality without the need for a central coordinator, thereby going beyond federated learning. To illustrate the feasibility of using Swarm Learning to develop disease classifiers using distributed data, we chose four use cases of heterogeneous diseases (COVID-19, tuberculosis, leukaemia and lung pathologies). With more than 16,400 blood transcriptomes derived from 127 clinical studies with non-uniform distributions of cases and controls and substantial study biases, as well as more than 95,000 chest X-ray images, we show that Swarm Learning classifiers outperform those developed at individual sites. In addition, Swarm Learning completely fulfils local confidentiality regulations by design. We believe that this approach will notably accelerate the introduction of precision medicine.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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    detail.hit.zdb_id: 1413423-8
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  • 4
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1006, No. 1 ( 2003-12), p. 122-132
    Abstract: A bstract : We fabricated three‐terminal devices with conjugated molecules. Two different device layouts were used to measure both very short molecules (with one or two benzene rings) and relatively long ones (as long as 8 nm). To achieve an optimum gate effect, we used aluminum gates covered with a very thin native oxide layer. Molecules with thiol end groups were positioned between the source and drain electrodes by self‐assembly. The device yield was low for short molecules, most likely due to defects in the self‐assembled monolayers. Most of the devices made with short molecules did not show any gate effect at all; a small gate effect was only observed in two samples made with 1,3‐benzenedithiol. Some devices showed clear negative differential conductance peaks. In some devices made with long molecules, we observed a small change of conductance with gate voltage.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
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    Language: English
    Publisher: Wiley
    Publication Date: 2003
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    detail.hit.zdb_id: 211003-9
    detail.hit.zdb_id: 2071584-5
    SSG: 11
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