Institution
University of California, Irvine
Education•Irvine, California, United States•
About: University of California, Irvine is a education organization based out in Irvine, California, United States. It is known for research contribution in the topics: Population & Galaxy. The organization has 47031 authors who have published 113602 publications receiving 5521832 citations. The organization is also known as: UC Irvine & UCI.
Topics: Population, Galaxy, Poison control, Cancer, Gene
Papers published on a yearly basis
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TL;DR: Observations that Aβ42 and other oligomers caused rapid cellular leakage of anionic fluorescent dyes point to a generalized increase in membrane permeability, which may provide a common mechanism for oligomer-mediated toxicity in many amyloidogenic diseases.
979 citations
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University of Texas MD Anderson Cancer Center1, Foundation Medicine2, Bristol-Myers Squibb3, Memorial Sloan Kettering Cancer Center4, Harvard University5, Novartis6, University of California, Irvine7, Tel Aviv University8, Rabin Medical Center9, Sarah Cannon Research Institute10, Brigham and Women's Hospital11, University of Hong Kong12, New York University13
TL;DR: Genomic profiling may enhance the predictive utility of PD-L1 expression and tumor mutation burden and facilitate establishment of personalized combination immunotherapy approaches for genomically defined LUAC subsets.
Abstract: KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) comutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine the efficacy of PD-1 inhibitors in these subgroups. Objective response rates to PD-1 blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) subgroups (P < 0.001) in the Stand Up To Cancer (SU2C) cohort (174 patients) with KRAS-mutant LUAC and in patients treated with nivolumab in the CheckMate-057 phase III trial (0% vs. 57.1% vs. 18.2%; P = 0.047). In the SU2C cohort, KL LUAC exhibited shorter progression-free (P < 0.001) and overall (P = 0.0015) survival compared with KRASMUT;STK11/LKB1WT LUAC. Among 924 LUACs, STK11/LKB1 alterations were the only marker significantly associated with PD-L1 negativity in TMBIntermediate/High LUAC. The impact of STK11/LKB1 alterations on clinical outcomes with PD-1/PD-L1 inhibitors extended to PD-L1-positive non-small cell lung cancer. In Kras-mutant murine LUAC models, Stk11/Lkb1 loss promoted PD-1/PD-L1 inhibitor resistance, suggesting a causal role. Our results identify STK11/LKB1 alterations as a major driver of primary resistance to PD-1 blockade in KRAS-mutant LUAC.Significance: This work identifies STK11/LKB1 alterations as the most prevalent genomic driver of primary resistance to PD-1 axis inhibitors in KRAS-mutant lung adenocarcinoma. Genomic profiling may enhance the predictive utility of PD-L1 expression and tumor mutation burden and facilitate establishment of personalized combination immunotherapy approaches for genomically defined LUAC subsets. Cancer Discov; 8(7); 822-35. ©2018 AACR.See related commentary by Etxeberria et al., p. 794This article is highlighted in the In This Issue feature, p. 781.
978 citations
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TL;DR: A reference, comprehensive, high-resolution, digital mosaic of ice motion in Antarctica assembled from multiple satellite interferometric synthetic-aperture radar data acquired during the International Polar Year 2007 to 2009 reveals widespread, patterned, enhanced flow with tributary glaciers reaching hundreds to thousands of kilometers inland over the entire continent.
Abstract: We present a reference, comprehensive, high-resolution, digital mosaic of ice motion in Antarctica assembled from multiple satellite interferometric synthetic-aperture radar data acquired during the International Polar Year 2007 to 2009. The data reveal widespread, patterned, enhanced flow with tributary glaciers reaching hundreds to thousands of kilometers inland over the entire continent. This view of ice sheet motion emphasizes the importance of basal-slip–dominated tributary flow over deformation-dominated ice sheet flow, redefines our understanding of ice sheet dynamics, and has far-reaching implications for the reconstruction and prediction of ice sheet evolution.
978 citations
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TL;DR: A phase 1 trial of ex vivo NGF gene delivery in eight individuals with mild Alzheimer disease, implanting autologous fibroblasts genetically modified to express human NGF into the forebrain found no long-term adverse effects and brain autopsy from one subject suggested robust growth responses to NGF.
Abstract: Cholinergic neuron loss is a cardinal feature of Alzheimer disease. Nerve growth factor (NGF) stimulates cholinergic function, improves memory and prevents cholinergic degeneration in animal models of injury, amyloid overexpression and aging. We performed a phase 1 trial of ex vivo NGF gene delivery in eight individuals with mild Alzheimer disease, implanting autologous fibroblasts genetically modified to express human NGF into the forebrain. After mean follow-up of 22 months in six subjects, no long-term adverse effects of NGF occurred. Evaluation of the Mini-Mental Status Examination and Alzheimer Disease Assessment Scale-Cognitive subcomponent suggested improvement in the rate of cognitive decline. Serial PET scans showed significant (P < 0.05) increases in cortical 18-fluorodeoxyglucose after treatment. Brain autopsy from one subject suggested robust growth responses to NGF. Additional clinical trials of NGF for Alzheimer disease are warranted.
977 citations
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TL;DR: The antagonistic pleiotropy theory proposes that certain alleles that are favoured because of beneficial early effects also have deleterious later effects, and the disposable soma theory suggests that because of the competing demands of reproduction less effort is invested in the maintenance of somatic tissues than is necessary for indefinite survival.
Abstract: In so far as it is associated with declining fertility and increasing mortality, senescence is directly detrimental to reproductive success. Natural selection should therefore act in the direction of postponing or eliminating senescence from the life history. The widespread occurrence of senescence is explained by observing that (i) the force of natural selection is generally weaker at late ages than at early ages, and (ii) the acquisition of greater longevity usually involves some cost. Two convergent theories are the ‘antagonistic pleiotropy’ theory, based in population genetics, and the ‘disposable soma’ theory, based in physiological ecology. The antagonistic pleiotropy theory proposes that certain alleles that are favoured because of beneficial early effects also have deleterious later effects. The disposable soma theory suggests that because of the competing demands of reproduction less effort is invested in the maintenance of somatic tissues than is necessary for indefinite survival.
977 citations
Authors
Showing all 47751 results
Name | H-index | Papers | Citations |
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Daniel Levy | 212 | 933 | 194778 |
Rob Knight | 201 | 1061 | 253207 |
Lewis C. Cantley | 196 | 748 | 169037 |
Dennis W. Dickson | 191 | 1243 | 148488 |
Terrie E. Moffitt | 182 | 594 | 150609 |
Joseph Biederman | 179 | 1012 | 117440 |
John R. Yates | 177 | 1036 | 129029 |
John A. Rogers | 177 | 1341 | 127390 |
Avshalom Caspi | 170 | 524 | 113583 |
Yang Gao | 168 | 2047 | 146301 |
Carl W. Cotman | 165 | 809 | 105323 |
John H. Seinfeld | 165 | 921 | 114911 |
Gregg C. Fonarow | 161 | 1676 | 126516 |
Jerome I. Rotter | 156 | 1071 | 116296 |
David Cella | 156 | 1258 | 106402 |