排序方式: 共有73条查询结果,搜索用时 31 毫秒
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Yu Qin Maoyong Fu Masamichi Takahashi Akio Iwanami Daisuke Kuga Rajiv G. Rao Deepthi Sudhakar Tiffany Huang Meagan Kiyohara Kathleen Torres Christen Dillard Akihito Inagaki Noriyuki Kasahara Lee Goodglick Jonathan Braun Paul S. Mischel Lynn K. Gordon Madhuri Wadehra 《The Journal of biological chemistry》2014,289(20):13974-13985
Despite recent advances in molecular classification, surgery, radiotherapy, and targeted therapies, the clinical outcome of patients with malignant brain tumors remains extremely poor. In this study, we have identified the tetraspan protein epithelial membrane protein-2 (EMP2) as a potential target for glioblastoma (GBM) killing. EMP2 had low or undetectable expression in normal brain but was highly expressed in GBM as 95% of patients showed some expression of the protein. In GBM cells, EMP2 enhanced tumor growth in vivo in part by up-regulating αvβ3 integrin surface expression, activating focal adhesion kinase and Src kinases, and promoting cell migration and invasion. Consistent with these findings, EMP2 expression significantly correlated with activated Src kinase in patient samples and promoted tumor cell invasion using intracranial mouse models. As a proof of principle to determine whether EMP2 could serve as a target for therapy, cells were treated using specific anti-EMP2 antibody reagents. These reagents were effective in killing GBM cells in vitro and in reducing tumor load in subcutaneous mouse models. These results support the role of EMP2 in the pathogenesis of GBM and suggest that anti-EMP2 treatment may be a novel therapeutic treatment. 相似文献
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Steven M. Silverstein Brian P. Keane Thomas V. Papathomas Kira L. Lathrop Hristian Kourtev Keith Feigenson Matthew W. Roché Yushi Wang Deepthi Mikkilineni Danielle Paterno 《PloS one》2014,9(12)
Low spatial frequency (SF) processing has been shown to be impaired in people with schizophrenia, but it is not clear how this varies with clinical state or illness chronicity. We compared schizophrenia patients (SCZ, n = 34), first episode psychosis patients (FEP, n = 22), and healthy controls (CON, n = 35) on a gender/facial discrimination task. Images were either unaltered (broadband spatial frequency, BSF), or had high or low SF information removed (LSF and HSF conditions, respectively). The task was performed at hospital admission and discharge for patients, and at corresponding time points for controls. Groups were matched on visual acuity. At admission, compared to their BSF performance, each group was significantly worse with low SF stimuli, and most impaired with high SF stimuli. The level of impairment at each SF did not depend on group. At discharge, the SCZ group performed more poorly in the LSF condition than the other groups, and showed the greatest degree of performance decline collapsed over HSF and LSF conditions, although the latter finding was not significant when controlling for visual acuity. Performance did not change significantly over time for any group. HSF processing was strongly related to visual acuity at both time points for all groups. We conclude the following: 1) SF processing abilities in schizophrenia are relatively stable across clinical state; 2) face processing abnormalities in SCZ are not secondary to problems processing specific SFs, but are due to other known difficulties constructing visual representations from degraded information; and 3) the relationship between HSF processing and visual acuity, along with known SCZ- and medication-related acuity reductions, and the elimination of a SCZ-related impairment after controlling for visual acuity in this study, all raise the possibility that some prior findings of impaired perception in SCZ may be secondary to acuity reductions. 相似文献
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Xiaoyong Bao Deepthi Kolli Junping Ren Tianshuang Liu Roberto P. Garofalo Antonella Casola 《PloS one》2013,8(4)
Human metapneumovirus (hMPV) is a recently identified RNA virus belonging to the Paramyxoviridae family. It is a common cause of respiratory tract infections in children, adults, and immunocompromised patients, for which no specific treatment or vaccine is available. Recent investigations in our lab identified hMPV glycoprotein G as an important virulence factor, as a recombinant virus lacking the G protein (rhMPV-ΔG) exhibited enhanced production of important immune and antiviral mediators, such as cytokines, chemokines and type I interferon (IFN) in airway epithelial cells, and expression of G protein alone inhibits cellular signaling dependent on retinoic induced gene (RIG)-I, a RNA helicase with a fundamental role in initiating hMPV-induced cellular responses. In this study, we have further investigated the mechanism underlying the inhibitory role of hMPV G protein on RIG-I-dependent signaling. We found that the interaction of hMPV G with RIG-I occurs primarily through the CARD domains of RIG-I N-terminus, preventing RIG-I association with the adaptor protein MAVS (mitochondrial antiviral signaling protein), recruitment of RIG-I to mitochondria, as well as the interaction between mitochondria and mitochondria-associated membrane (MAM) component of the endoplasmic reticulum (ER), which contains STINGS, an important part of the viral-induced RIG-I/MAVS signaling pathway, leading in the end to the inhibition of cytokine, chemokine and type I IFN expression. Mutagenesis analysis showed that hMPV G protein cytoplasmic domain played a major role in the observed inhibitory activity, and recombinant viruses expressing a G protein with amino acid substitution in position 2 and 3 recapitulated most of the phenotype observed with rhMPV-ΔG mutant upon infection of airway epithelial cells. 相似文献
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Naomi Ohta Susumu Ishiguro Atsushi Kawabata Deepthi Uppalapati Marla Pyle Deryl Troyer Supriyo De Yongqing Zhang Kevin G. Becker Masaaki Tamura 《PloS one》2015,10(5)
Human and rat umbilical cord matrix mesenchymal stem cells (UCMSC) possess the ability to control the growth of breast carcinoma cells. Comparative analyses of two types of UCMSC suggest that rat UCMSC-dependent growth regulation is significantly stronger than that of human UCMSC. Their different tumoricidal abilities were clarified by analyzing gene expression profiles in the two types of UCMSC. Microarray analysis revealed differential gene expression between untreated naïve UCMSC and those co-cultured with species-matched breast carcinoma cells. The analyses screened 17 differentially expressed genes that are commonly detected in both human and rat UCMSC. The comparison between the two sets of gene expression profiles identified two tumor suppressor genes, adipose-differentiation related protein (ADRP) and follistatin (FST), that were specifically up-regulated in rat UCMSC, but down-regulated in human UCMSC when they were co-cultured with the corresponding species’ breast carcinoma cells. Over-expression of FST, but not ADRP, in human UCMSC enhanced their ability to suppress the growth of MDA-231 cells. The growth of MDA-231 cells was also significantly lower when they were cultured in medium conditioned with FST, but not ADRP over-expressing human UCMSC. In the breast carcinoma lung metastasis model generated with MDA-231 cells, systemic treatment with FST-over-expressing human UCMSC significantly attenuated the tumor burden. These results suggest that FST may play an important role in exhibiting stronger tumoricidal ability in rat UCMSC than human UCMSC and also implies that human UCMSC can be transformed into stronger tumoricidal cells by enhancing tumor suppressor gene expression. 相似文献
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Background
Respiratory syncytial virus (RSV) is the leading cause of respiratory infections in children, elderly, and immunocompromised individuals. Severe infection is associated with short- and long-term morbidity including pneumonia, recurrent wheezing, and abnormal pulmonary function, and several lines of evidence indicate that impaired adaptive immune responses during infection are critical in the pathophysiology of RSV-mediated disease. Myeloid Dendritic cells (mDCs) play a pivotal role in shaping antiviral immune responses in the respiratory tract; however, few studies have examined the interactions between RSV and individual mDC subsets. In this study, we examined the effect of RSV on the functional response of primary mDC subsets (BDCA-1+ and BDCA-3+) isolated from peripheral blood.Methods
BDCA-1+ and BDCA-3+ mDCs were isolated from the peripheral blood of healthy adults using FACS sorting. Donor-matched BDCA-1+ and BDCA-3+ mDCs were infected with RSV at a multiplicity of infection (MOI) of 5 for 40 hours. After infection, cells were analyzed for the expression of costimulatory molecules (CD86, CD80, and PD-L1), cytokine production, and the ability to stimulate allogenic CD4+ T cell proliferation.Results
Both BDCA-1+ and BDCA-3+ mDCs were susceptible to infection with RSV and demonstrated enhanced expression of CD86, and the inhibitory costimulatory molecules CD80 and PD-L1. Compared to BDCA-3+ mDCs, RSV-infected BDCA-1+ mDC produced a profile of cytokines and chemokines predominantly associated with pro-inflammatory responses (IL-1β, IL-6, IL-12, MIP-1α, and TNF-α), and both BDCA-1+ and BDCA-3+ mDCs were found to produce IL-10. Compared to uninfected mDCs, RSV-infected BDCA-1+ and BDCA-3+ mDCs demonstrated a reduced capacity to stimulate T cell proliferation.Conclusions
RSV infection induces a distinct pattern of costimulatory molecule expression and cytokine production by BDCA-1+ and BDCA-3+ mDCs, and impairs their ability to stimulate T cell proliferation.The differential expression of CD86 and pro-inflammatory cytokines by highly purified mDC subsets in response to RSV provides further evidence that BDCA-1+ and BDCA-3+ mDCs have distinct roles in coordinating the host immune response during RSV infection. Findings of differential expression of PD-L1 and IL-10 by infected mDCs, suggests possible mechanisms by which RSV is able to impair adaptive immune responses. 相似文献19.
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Assassi S Leyva AL Mayes MD Sharif R Nair DK Fischbach M Nguyen N Reveille JD Gonzalez EB McNearney TA;GENISOS Study Group 《PloS one》2011,6(10):e26061