Rmed research. D.G. and J.J.W. contributed reagents and analytic tools. V.V., J.J.W., and J.J.K. analyzed data. V.V., D.G., D.C., S.E.B., J.J.W., and J.J.K. wrote and reviewed the manuscript. Competing interests: The authors declare that they’ve no competing interests. Data and supplies availability: All information needed to evaluate the conclusions in the paper are present within the paper andor the Supplementary Materials. Further data associated to this paper may well be requested from the authors.Submitted 18 May well 2016 Accepted 5 October 2016 Published four November 2016 10.1126sciadv.1601132 Citation: V. Vidimar, D. Gius, D. Chakravarti, S. E. Bulun, J.J. Wei, J. J. Kim, Dysfunctional MnSOD results in redox dysregulation and activation of prosurvival AKT signaling in uterine leiomyomas. Sci. Adv. 2, e1601132 (2016).Vidimar et al. Sci. Adv. 2016; 2 : e4 November11 of
Gao et al. BMC Cancer 2013, 13:471 http:www.biomedcentral.com1471240713RESEARCH ARTICLEOpen Accessprognostic significance and therapeutic potential in the activation of anaplastic lymphoma kinaseprotein kinase Bmammalian target of rapamycin signaling pathway in anaplastic big cell lymphomaJu Gao1, Minzhi Yin2, Yiping Zhu1, Ling Gu1, Yanle Zhang1, Qiang Li1, Cangsong Jia1 and Zhigui Ma1AbstractBackgroud: Activation on the protein kinase Bmammalian target of rapamycin (AKTmTOR) pathway has been demonstrated to become involved in nucleophosminanaplastic lymphoma kinase (NPMALK)mediated tumorigenesis in anaplastic large cell lymphoma (ALCL) and correlated with unfavorable outcome in certain kinds of other cancers. Even so, the prognostic worth of L-Cysteine Endogenous Metabolite AKTmTOR activation in ALCL remains to become totally elucidated. Within the present study, we aim to address this question from a clinical perspective by comparing the Liarozole Epigenetic Reader Domain expressions on the AKTmTOR signaling molecules in ALCL sufferers and exploring the therapeutic significance of targeting the AKTmTOR pathway in ALCL. Approaches: A cohort of 103 patients with ALCL was enrolled in the study. Expression of ALK fusion proteins and the AKTmTOR signaling phosphoproteins was studied by immunohistochemical (IHC) staining. The pathogenic role of ALK fusion proteins and the therapeutic significance of targeting the ATKmTOR signaling pathway have been additional investigated in vitro study with an ALK ALCL cell line and the NPMALK transformed BaF3 cells. Outcomes: ALK expression was detected in 60 of ALCLs, of which 79 exhibited the presence of NPMALK, whereas the remaining 21 expressed variantALK fusions. Phosphorylation of AKT, mTOR, 4Ebinding protein1 (4EBP1), and 70 kDa ribosomal protein S6 kinase polypeptide 1 (p70S6K1) was detected in 76 , 80 , 91 , and 93 of ALCL sufferers, respectively. Each phosphoAKT (pAKT) and pmTOR were correlated to ALK expression, and pmTOR was closely correlated to pAKT. Both p4EBP1 and pp70S6K1 were correlated to pmTOR, but have been not correlated towards the expression of ALK and pAKT. Clinically, ALK ALCL occurred extra frequently in younger individuals, and ALK ALCL patients had a a great deal far better prognosis than ALKALCL cases. Having said that, expression of pAKT, pmTOR, p4EBP1, or pp70S6K1 did not have an influence on the clinical outcome. Overexpression of NPMALK in a nonmalignant murine proB lymphoid cell line, BaF3, induced the cells to come to be cytokineindependent and resistant to glucocorticoids (GCs). Targeting AKTmTOR inhibited development and triggered the apoptotic cell death of ALK ALCL cells and NPMALK transformed BaF3 cells, and also reversed GC resistance induced by ov.
