Abstract:
:For many intraoperative decisions surgeons depend on frozen section pathology, a technique developed over 150 y ago. Technical innovations that permit rapid molecular characterization of tissue samples at the time of surgery are needed. Here, using desorption electrospray ionization (DESI) MS, we rapidly detect the tumor metabolite 2-hydroxyglutarate (2-HG) from tissue sections of surgically resected gliomas, under ambient conditions and without complex or time-consuming preparation. With DESI MS, we identify isocitrate dehydrogenase 1-mutant tumors with both high sensitivity and specificity within minutes, immediately providing critical diagnostic, prognostic, and predictive information. Imaging tissue sections with DESI MS shows that the 2-HG signal overlaps with areas of tumor and that 2-HG levels correlate with tumor content, thereby indicating tumor margins. Mapping the 2-HG signal onto 3D MRI reconstructions of tumors allows the integration of molecular and radiologic information for enhanced clinical decision making. We also validate the methodology and its deployment in the operating room: We have installed a mass spectrometer in our Advanced Multimodality Image Guided Operating (AMIGO) suite and demonstrate the molecular analysis of surgical tissue during brain surgery. This work indicates that metabolite-imaging MS could transform many aspects of surgical care.
journal_name
Proc Natl Acad Sci U S Aauthors
Santagata S,Eberlin LS,Norton I,Calligaris D,Feldman DR,Ide JL,Liu X,Wiley JS,Vestal ML,Ramkissoon SH,Orringer DA,Gill KK,Dunn IF,Dias-Santagata D,Ligon KL,Jolesz FA,Golby AJ,Cooks RG,Agar NYdoi
10.1073/pnas.1404724111subject
Has Abstractpub_date
2014-07-29 00:00:00pages
11121-6issue
30eissn
0027-8424issn
1091-6490pii
1404724111journal_volume
111pub_type
临床试验,杂志文章abstract::Mouse bone marrow-derived Lin(-)-Sca-1(+) endothelial progenitor cell (EPC) has pluripotent abilities such as supporting neovascularization. Vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1) (Flt1) recognizes various VEGF isoforms and is critically implicated in a wide range of physiological and pathologic...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1304529110
更新日期:2013-08-20 00:00:00
abstract::Tropical birds are relatively long-lived and produce few offspring, which develop slowly and mature relatively late in life, the slow end of the life-history axis, whereas temperate birds lie at the opposite end of this continuum. We tested the hypothesis that tropical birds have evolved a reduced basal metabolic rate...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0702212104
更新日期:2007-05-29 00:00:00
abstract::The objective of this study was to determine whether the vascular smooth muscle contractile effect of NG-methyl-L-arginine (NMA) is endothelium dependent and attributed to a decline in smooth muscle levels of cyclic GMP. Vascular smooth muscle levels of cyclic GMP are severalfold greater in endothelium-intact than in ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.12.4430
更新日期:1990-06-01 00:00:00
abstract::Mechanisms for controlling symbiont populations are critical for maintaining the associations that exist between a host and its microbial partners. We describe here the transcriptional, metabolic, and ultrastructural characteristics of a diel rhythm that occurs in the symbiosis between the squid Euprymna scolopes and ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0909712107
更新日期:2010-02-02 00:00:00
abstract::Recent studies with fibroblasts have shown that peptidylhydroxyproline formation begins toward the end of the log phase of growth and is an expression of the activity of the enzyme, collagen proline hydroxylase, which increase in late log-phase cells. This communication reports a two- to fivefold increase in hydroxyla...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.66.2.552
更新日期:1970-06-01 00:00:00
abstract::Metal-inducible transcription of metallothionein (MT) genes involves the interaction of metal-responsive trans-acting factors with specific promoter DNA sequence elements. In this report, we present a genetic selection using the baker's yeast, Saccharomyces cerevisiae, to clone a gene from Candida glabrata encoding a ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.14.6112
更新日期:1991-07-15 00:00:00
abstract::Oligomerization plays a critical role in shaping the light-harvesting properties of many photosynthetic pigment-protein complexes, but a detailed understanding of this process at the level of individual pigments is still lacking. To study the effects of oligomerization, we designed a single-molecule approach to probe ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1514027112
更新日期:2015-11-10 00:00:00
abstract::Neonates are highly susceptible to infectious diseases and, in general, respond poorly to conventional vaccines due to immaturity of the immune system. In the present study, we hypothesized that the anti-tetanus toxoid (TT) vaccine response of neonatal mice could be enhanced by retinoic acid (RA), a bioactive retinoid...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0506438102
更新日期:2005-09-20 00:00:00
abstract::Intestinal trefoil factor (ITF) is an essential regulator of colonic epithelial restitution, the rapid migration of colonocytes over mucosal wounds. High levels of ITF are frequently present in colorectal cancers and derived cell lines. Mucosal restitution requires the detachment of epithelium from substrate, which wo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.2.799
更新日期:2000-01-18 00:00:00
abstract::Mutations in fibroblast growth factor receptor 2 (FGFR2) and its ligand, FGF10, are known to cause lacrimo-auriculo-dento-digital (LADD) syndrome. Multiple gain-of-function mutations in FGF receptors have been implicated in a variety of severe skeletal disorders and in many cancers. We aimed to elucidate the mechanism...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0709905104
更新日期:2007-12-11 00:00:00
abstract::We report light-induced electron paramagnetic resonance triplet spectra from samples of chloroplasts or digitonin photosystem I particles that depend upon the dark redox state of the bound acceptors of photosystem I. If the reaction centers are prepared in the redox state P-700 A X- FdB-FdA-, then upon illumination at...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.10.5124
更新日期:1979-10-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.7.4584
更新日期:1981-07-01 00:00:00
abstract::Oxidants, such as those generated by metabolically activated phagocytes in inflammation, have been implicated in the metabolic activation of carcinogens, and in this study we demonstrate that the interaction of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP 7,8-dihydrodiol) with phorbol ester-stimulated polym...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.15.5194
更新日期:1985-08-01 00:00:00
abstract::A 1H NMR study of the 79-residue globular domain of chicken erythrocyte histone H5 (GH5) is presented. Using a combination of two-dimensional NMR techniques to demonstrate through-bond and through-space (less than 5 A) connectivities, the resonances of GH5 are assigned in a sequential manner. From a qualitative interp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.20.7628
更新日期:1986-10-01 00:00:00
abstract::Polymorphism may play an important role in speciation because new species could originate from the distinctive morphs observed in polymorphic populations. However, much remains to be understood about the process by which morphs found new species. To detail the steps of this mode of speciation, we studied the geographi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0909480107
更新日期:2010-03-02 00:00:00
abstract::Type 2 diabetes mellitus (T2DM) is strongly associated with obesity in most, but not all, ethnic groups, suggesting important ethnic differences in disease susceptibility. Although it is clear that insulin resistance plays a major role in the pathogenesis of T2DM and that insulin resistance is strongly associated with...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0608537103
更新日期:2006-11-28 00:00:00
abstract::Circadian rhythms modulate many aspects of physiology. Knowledge of the molecular basis of these rhythms has exploded in the last 20 years. However, most of these data are from model organisms, and translation to clinical practice has been limited. Here, we present an approach to identify molecular rhythms in humans f...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1619320114
更新日期:2017-05-16 00:00:00
abstract::Calcitonin gene-related peptide (CGRP) is a neuropeptide that coexists with acetylcholine in spinal cord motoneurons. The effects of CGRP on the functional properties of the nicotinic acetylcholine receptor (AcChoR) were examined by electrophysiological methods. Using the whole-cell patch-clamp technique and a mouse c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.15.5728
更新日期:1988-08-01 00:00:00
abstract::Sexual arousal is a dynamical, highly coordinated neurophysiological process that is often induced by visual stimuli. Numerous studies have proposed that the cognitive processing stage of responding to sexual stimuli is the first stage, in which sex differences occur, and the divergence between men and women has been ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,meta分析
doi:10.1073/pnas.1904975116
更新日期:2019-07-30 00:00:00
abstract::The coordinated redistribution of sugars from mature "source" leaves to developing "sink" leaves requires tight regulation of sugar transport between cells via plasmodesmata (PD). Although fundamental to plant physiology, the mechanisms that control PD transport and thereby support development of new leaves have remai...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1919196117
更新日期:2020-03-03 00:00:00
abstract::We investigated the participation of genomic regulatory events in the response of the songbird brain to a natural auditory stimulus of known physiological and behavioral relevance, birdsong. Using in situ hybridization, we detected a rapid increase in forebrain mRNA levels of an immediate-early gene encoding a transcr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.15.6818
更新日期:1992-08-01 00:00:00
abstract::Fifty cats with feline leukemia virus (FeLV) infection and leukemia-lymphoma complex were treated by ex vivo immunoadsorption with Staphylococcus protein A-bound filters. Most cats responded to therapy. Twelve showed tumor regression, including disappearance of tumor cells, but died later of other complications. Three...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.11.3516
更新日期:1984-06-01 00:00:00
abstract::Initial attempts to correlate the distribution of gene density (number of gene loci per unit length on the linkage map) with the distribution of lengths of coding sequences have led to the observation that 46% of approximately 1000 sampled proteins in Escherichia coli have molecular masses of n X 14,000 +/- 2500 dalto...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.5.1198
更新日期:1986-03-01 00:00:00
abstract::The crystal structure of the murine Fab S-20-4 from a protective anti-cholera Ab specific for the lipopolysaccharide Ag of the Ogawa serotype has been determined in its unliganded form and in complex with synthetic fragments of the Ogawa O-specific polysaccharide (O-SP). The upstream terminal O-SP monosaccharide is sh...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.060022997
更新日期:2000-07-18 00:00:00
abstract::Mutations at position 187 in secreted gelsolin enable aberrant proteolysis at the 172-173 and 243-244 amide bonds, affording the 71-residue amyloidogenic peptide deposited in Familial Amyloidosis of Finnish Type (FAF). Thermodynamic comparisons of two different domain 2 constructs were carried out to study possible ef...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.041452598
更新日期:2001-02-27 00:00:00
abstract::We present whole-genome assemblies of four divergent Arabidopsis thaliana strains that complement the 125-Mb reference genome sequence released a decade ago. Using a newly developed reference-guided approach, we assembled large contigs from 9 to 42 Gb of Illumina short-read data from the Landsberg erecta (Ler-1), C24,...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1107739108
更新日期:2011-06-21 00:00:00
abstract::We investigated the effect of actin filament barbed end uncapping on Arp23 complex function both in vivo and in vitro. Arp23 complex redistributes rapidly and uniformly to the lamellar edge of activated wild-type platelets and fibroblasts but clusters in marginal actin filament clumps in gelsolin-null cells. Treatment...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.222652499
更新日期:2002-12-24 00:00:00
abstract::It recently has been shown that epithelial Na(+) channels are controlled by a receptor for intracellular Na(+), a G protein (G(o)), and a ubiquitin-protein ligase (Nedd4). Furthermore, mutations in the epithelial Na(+) channel that underlie the autosomal dominant form of hypertension known as Liddle's syndrome inhibit...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.17.9949
更新日期:1999-08-17 00:00:00
abstract::Mechanisms that control the levels and activities of reactive oxygen species (ROS) in normal human mammary cells are poorly understood. We show that purified normal human basal mammary epithelial cells maintain low levels of ROS primarily by a glutathione-dependent but inefficient antioxidant mechanism that uses mitoc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1403813111
更新日期:2014-05-27 00:00:00
abstract::The sequence of the cloned Bacillus amyloliquefaciens subtilisin gene suggested that this secreted serine protease is produced as a larger precursor, designated preprosubtilisin [Wells, J. A., Ferrari, E., Henner, D. J., Estell, D. A. & Chen, E. Y. (1983) Nucleic Acids Res. 11, 7911-7925]. Biochemical evidence present...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.10.3096
更新日期:1986-05-01 00:00:00