101 research outputs found

    Fragmentation of High-Spin Particle-Hole States in 26-Mg

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    This work was supported by the National Science Foundation Grants NSF PHY 78-22774 A03, NSF PHY 81-14339, and by Indiana Universit

    Fragmentation of High-spin Particle-hole States in 26-Mg

    Get PDF
    This research was sponsored by the National Science Foundation Grant NSF PHy 87-1440

    Fragmentation of High-Spin Particle-Hole States in 26-Mg

    Get PDF
    This work was supported by the National Science Foundation Grant NSF PHY 81-14339 and by Indiana Universit

    Tradeoff between metabolic i-proteasome addiction and immune evasion in triple-negative breast cancer

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    In vitro studies have suggested proteasome inhibitors could be effective in triple-negative breast cancer (TNBC). We found that bortezomib and carfilzomib induce proteotoxic stress and apoptosis via the unfolded protein response (UPR) in TNBC cell lines, with sensitivity correlated with expression of immuno-(PSMB8/9/10) but not constitutive-(PSMB5/6/7) proteasome subunits. Equally, the transcriptomes of i-proteasome-high human TNBCs are enriched with UPR gene sets, and the genomic copy number landscape reflects positive selection pressure favoring i-proteasome activity, but in the setting of adjuvant treatment, this is actually associated with favorable prognosis. Tumor expression of PSMB8 protein (β5i) is associated with levels of MHC-I, interferon-γ-inducible proteasome activator PA28β, and the densities of stromal antigen-presenting cells and lymphocytes (TILs). Crucially, TILs were protective among TNBCs that maintain high β5i but did not stratify survival amongst β5i-low TNBCs. Moreover, β5i expression was lower in brain metastases than in patient-matched primary breast tumors (n = 34; P = 0.007), suggesting that suppression contributes to immune evasion and metastatic progression. Hence, inhibiting proteasome activity could be counterproductive in the adjuvant treatment setting because it potentiates anti-TNBC immunity.Alaknanda Adwal, Priyakshi Kalita-de Croft, Reshma Shakya, Malcolm Lim, Emarene Kalaw, Lucinda D Taege, Amy E McCart Reed, Sunil R Lakhani, David F Callen, Jodi M Saunu
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