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排序方式: 共有118条查询结果,搜索用时 31 毫秒
61.
Durinck S Ho C Wang NJ Liao W Jakkula LR Collisson EA Pons J Chan SW Lam ET Chu C Park K Hong SW Hur JS Huh N Neuhaus IM Yu SS Grekin RC Mauro TM Cleaver JE Kwok PY LeBoit PE Getz G Cibulskis K Aster JC Huang H Purdom E Li J Bolund L Arron ST Gray JW Spellman PT Cho RJ 《Cancer discovery》2011,1(2):137-143
Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for 2 separate cancer types. We detect vast, unreported expansion of simple mutations sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCC) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes. 相似文献
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Mutant Escherichia coli heat-labile toxin B subunit that separates toxoid-mediated signaling and immunomodulatory action from trafficking and delivery functions 总被引:3,自引:0,他引:3
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Fraser SA de Haan L Hearn AR Bone HK Salmond RJ Rivett AJ Williams NA Hirst TR 《Infection and immunity》2003,71(3):1527-1537
The homopentameric B-subunit components of Escherichia coli heat-labile enterotoxin (EtxB) and cholera toxin (CtxB) possess the capacity to enter mammalian cells and to activate cell-signaling events in leukocytes that modulate immune cell function. Both properties have been attributed to the ability of the B subunits to bind to GM1-ganglioside receptors, a ubiquitous glycosphingolipid found in the plasma membrane. Here we describe the properties of EtxB(H57S), a mutant B subunit with a His-->Ser substitution at position 57. The mutant was found to be severely defective in inducing leukocyte signaling, as shown by failure to (i) trigger caspase 3-mediated CD8(+)-T-cell apoptosis, (ii) activate nuclear translocation of NF-kappaB in Jurkat T cells, (iii) induce a potent anti-B-subunit response in mice, or (iv) serve as a mucosal adjuvant. However, its GM1 binding, cellular uptake, and delivery functions remained intact. This was further validated by the finding that EtxB(H57S) was as effective as EtxB in delivering a conjugated model class I epitope into the major histocompatibility complex class I pathway of a dendritic cell line. These observations imply that GM1 binding alone is not sufficient to trigger the signaling events responsible for the potent immunomodulatory properties of EtxB. Moreover, they demonstrate that its signaling properties play no role in EtxB uptake and trafficking. Thus, EtxB(H57S) represents a novel tool for evaluating the complex cellular interactions and signaling events occurring after receptor interaction, as well as offering an alternative means of delivering attached peptides in the absence of the potent immunomodulatory signals induced by wild-type B subunits. 相似文献
65.
Son NH Joyce B Hieatt A Chrest FJ Yanovski J Weng NP 《Mechanisms of ageing and development》2003,124(4):427-432
Telomere length and telomerase activity play important roles in regulating replicative lifespan of cells. The length of telomeres also serves as a marker for the replicative history and for the remaining replicative potential of cells. Differential telomere length has been reported in human na?ve and memory T cells but not in na?ve versus memory B-lymphocytes. We report here an analysis of telomere length and induced telomerase expression in na?ve (CD27(-)) and memory (CD27(+)) B cells from normal adults. Although both na?ve and memory B cells lose telomere repeats with age, there is no consistent difference in telomere length between these two B cell subsets. Furthermore, both na?ve and memory B cells are capable of inducing telomerase activity at similar levels after in vitro stimulation independent of donor's age. Finally, there is a slow increase of memory B cells in peripheral blood with age. Together, these findings suggest that B cells are capable of maintaining telomere length during differentiation from na?ve to memory B cells and this ability is maintained through age. 相似文献
66.
Oliver C Murphy G Hall S Arron K Leggett J 《American journal of mental retardation : AJMR》2003,108(2):71-81
Self-restraint is often reported in individuals with mental retardation who show self-injurious behavior (SIB). In this study, the phenomenology and prevalence of self-restraint in individuals showing self-injury and wearing protective devices and those showing self-injury but not wearing protective devices were compared. A high prevalence of self-restraint in the whole sample of individuals showing self-injury was identified (67/88, 76.1%), and self-restraint was more prevalent in a group showing self-injury but not wearing protective devices (43/47, 91.5%) than in a group showing self-injury and wearing protective devices (24/41, 58.5%). Individuals not wearing protective devices showed a greater number of topographies of self-restraint than those who did wear them. Results are discussed with reference to the purely topographical definition of self-restraint employed and the potential equivalence of protective devices and self-restraint. 相似文献
67.
Fas(CD95) and its ligand (FasL) interaction plays a pivotal role in T cell receptor (TCR)-mediated apoptosis. However, the susceptibility of T cells to Fas-mediated apoptosis is tightly regulated during immune responses, a regulation which is thought to maintain the antigen-specificity of T cell apoptosis. Here we show that TCR stimulation enhances the induction of Fas-mediated apoptosis. In addition, using a mutant T cell hybridoma with impaired FasL expression, we show that the synergy provided by TCR stimulation can be mimicked by activators of PKC but not calcium influx. This effect cannot be inhibited by actinomycin D, suggesting that TCR stimulation leads to the alteration in preexisting signaling molecules to enhance Fas-mediated apoptosis. Our results therefore provide a mechanism of how Fas-FasL interactions lead to T cell death in an antigen-specific manner via repetitive antigen stimulation. 相似文献
68.
Major prognostic factors for recurrence and survival independent of the American Joint Committee on Cancer eighth edition staging system in patients with cutaneous squamous cell carcinoma treated with multimodality therapy
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69.
Daniel E. Speiser Soo Young Lee Brian Wong Joseph Arron Angela Santana Young-Yun Kong Pamela S. Ohashi Yongwon Choi 《The Journal of experimental medicine》1997,185(10):1777-1783
Tumor necrosis factor receptor (TNFR)–associated factor 2 (TRAF2) and TRAF1 were found as components of the TNFR2 signaling complex, which exerts multiple biological effects on cells such as cell proliferation, cytokine production, and cell death. In the TNFR2-mediated signaling pathways, TRAF2 works as a mediator for activation signals such as NF-κB, but the role of TRAF1 has not been previously determined. Here we show in transgenic mice that TRAF1 overexpression inhibits antigen-induced apoptosis of CD8+ T lymphocytes. Our results demonstrate a biological role for TRAF1 as a regulator of apoptotic signals and also support the hypothesis that the combination of TRAF proteins in a given cell type determines distinct biological effects triggered by members of the TNF receptor superfamily. 相似文献