Abstract:
:Multiplex assays, involving the simultaneous use of multiple circulating tumor DNA (ctDNA) markers, can improve the performance of liquid biopsies so that they are highly predictive of cancer recurrence. We have developed a single-tube methylation-specific quantitative PCR assay (mqMSP) that uses 10 different methylation markers and is capable of quantitative analysis of plasma samples with as little as 0.05% tumor DNA. In a cohort of 179 plasma samples from colorectal cancer (CRC) patients, adenoma patients, and healthy controls, the sensitivity and specificity of the mqMSP assay were 84.9% and 83.3%, respectively. In a head-to-head comparative study, the mqMSP assay also performed better for detecting early-stage (stage I and II) and premalignant polyps than a published SEPT9 assay. In an independent longitudinal cohort of 182 plasma samples (preoperative, postoperative, and follow-up) from 82 CRC patients, the mqMSP assay detected ctDNA in 73 (89.0%) of the preoperative plasma samples. Postoperative detection of ctDNA (within 2 wk of surgery) identified 11 of the 20 recurrence patients and was associated with poorer recurrence-free survival (hazard ratio, 4.20; P = 0.0005). With subsequent longitudinal monitoring, 14 patients (70%) had detectable ctDNA before recurrence, with a median lead time of 8.0 mo earlier than seen with radiologic imaging. The mqMSP assay is cost-effective and easily implementable for routine clinical monitoring of CRC recurrence, which can lead to better patient management after surgery.
journal_name
Proc Natl Acad Sci U S Aauthors
Jin S,Zhu D,Shao F,Chen S,Guo Y,Li K,Wang Y,Ding R,Gao L,Ma W,Lu T,Li D,Zhang Z,Cai S,Liang X,Song H,Ji L,Li J,Zheng Z,Jiang F,Wu X,Luan J,Zhang H,Yang Z,Cantor CR,Xu C,Ding Cdoi
10.1073/pnas.2017421118subject
Has Abstractpub_date
2021-02-02 00:00:00issue
5eissn
0027-8424issn
1091-6490pii
2017421118journal_volume
118pub_type
杂志文章abstract::We have determined the nucleotide sequence of the dihydrofolate reductase-thymidylate synthetase (DHFR-TS) gene of the protozoan parasite Leishmania major (dihydrofolate reductase, EC 1.5.1.3 and thymidylate synthase, EC 2.1.1.45). The DHFR-TS protein is encoded by a single 1560-base-pair open reading frame within gen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.83.8.2584
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abstract::Unintended anthropogenic deposition of sulfur (S) to forest ecosystems has a range of negative consequences, identified through decades of research. There has been far less study of purposeful S use in agricultural systems around the world, including the application of elemental sulfur (S(0)) as a quick-reacting fungi...
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.1110741108
更新日期:2011-08-23 00:00:00
abstract::A Raleigh, NC, population of Drosophila melanogaster was sampled for the presence of enzyme null alleles at 25 loci. No nulls were found at any of five X-linked loci. Nulls were recovered at 13 of 20 autosomal loci; the weighted mean frequency for all 20 autosomal loci was estimated to be 0.0025. A consideration of th...
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.77.2.1091
更新日期:1980-02-01 00:00:00
abstract::We report on a fundamental technological advance for multilayer polydimethylsiloxane (PDMS) microfluidics. Vertical passages (vias), connecting channels located in different layers, are fabricated monolithically, in parallel, by simple and easy means. The resulting 3D connectivity greatly expands the potential complex...
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.0602890103
更新日期:2006-08-15 00:00:00
abstract::Stearic acid is toxic for T lymphocytes in vitro but has little effect on B lymphocytes. To investigate the molecular basis for this difference, purified murine T and B lymphocytes were compared for their abilities to incorporate and metabolize stearic acid. Unstimulated T and B cells incorporated identical amounts of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.86.16.6133
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abstract::The Sleeping Beauty (SB) transposon system can integrate foreign sequences of DNA in the genome of mouse somatic cells eliciting long-term expression in vivo. This technology holds great promise for human gene therapy as a nonviral technology to deliver therapeutic genes. SB also provides a means to study the effects ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.0502974102
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.0909954106
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abstract::The clinical efficacy of local anesthetic and antiarrhythmic drugs is due to their voltage- and frequency-dependent block of Na+ channels. Quaternary local anesthetic analogs such as QX-314, which are permanently charged and membrane-impermeant, effectively block cardiac Na+ channels when applied from either side of t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.92.25.11839
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::Bacterial outer membrane porins have a robust beta-barrel structure and therefore show potential for use as stochastic sensors based on single-molecule detection. The monomeric porin OmpG is especially attractive compared with multisubunit proteins because appropriate modifications of the pore can be easily achieved b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.0711561105
更新日期:2008-04-29 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.2131819100
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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.0802864106
更新日期:2009-03-03 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::Symbiotic microbes impact the severity of a variety of diseases through regulation of T-cell development. However, little is known regarding the molecular mechanisms by which this is accomplished. Here we report that a secreted factor, Erdr1, is regulated by the microbiota to control T-cell apoptosis. Erdr1 expression...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.1619336114
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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.0809090105
更新日期:2008-11-04 00:00:00
abstract::The population genetic consequences of nearest-neighbor pollination in an outcrossing plant species were investigated through computer simulations. The genetic system consisted of two alleles at a single locus in a self-incompatible plant that mates by random pollen transfer from a neighboring individual. Beginning wi...
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.79.1.203
更新日期:1982-01-01 00:00:00
abstract::Two chlorophyll-protein complexes associated with photosystem II (PSII) of the cyanobacterium Anacystis nidulans R2 have been detected. The larger of the two complexes, CPVI-1, contained a 71-kDa and a 42-kDa protein. The 71-kDa protein was determined to be the anchor protein of the phycobilisomes (the light-harvestin...
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.82.20.6903
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abstract::Regulation of the turnover of triglycerides in adipose tissue requires the continuous provision of 3-glycerophosphate, which may be supplied by the metabolism of glucose or by glyceroneogenesis, the de novo synthesis of 3-glycerophosphate from sources other than hexoses or glycerol. The importance of glyceroneogenesis...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::Recent data indicate that sustained elevations in plasma insulin suppress the mRNA for IRS-2, a component of the insulin signaling pathway in liver, and that this deficiency contributes to hepatic insulin resistance and inappropriate gluconeogenesis. Here, we use nuclear run-on assays to show that insulin inhibits tra...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2001-09-25 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.69.11.3105
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abstract::We have developed a high-efficiency nucleic acid delivery system that uses receptor-mediated endocytosis to carry DNA macromolecules into cells. We accomplished this by conjugating the iron-transport protein transferrin to polycations that bind nucleic acids. Human transferrin, as well as the chicken homologue conalbu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.87.9.3410
更新日期:1990-05-01 00:00:00
abstract::Persistent organic pollutants (POPs) have been associated with a wide range of adverse health effects. Our case-control study was performed to explore the association between placental levels of selected POPs and risks for neural tube defects (NTDs) in a Chinese population with a high prevalence of NTDs. Cases include...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.1105209108
更新日期:2011-08-02 00:00:00
abstract::Nonribosomal peptides and polyketides are a diverse group of natural products with complex chemical structures and enormous pharmaceutical potential. They are synthesized on modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzyme complexes by a conserved thiotemplate mechanism. Here, we rep...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.1401734111
更新日期:2014-06-24 00:00:00
abstract::The number of large intramembrane particles associated with sites of synaptic vesicle release at the squid giant synapse was determined and compared to the average maximal presynaptic calcium current in order to derive an estimate of the conductance each particle would have if it were a calcium channel. This value, 0....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.78.11.7210
更新日期:1981-11-01 00:00:00
abstract::After more than a decade of experiments generating and studying the physics of quantized vortices in atomic gas Bose-Einstein condensates, research is beginning to focus on the roles of vortices in quantum turbulence, as well as other measures of quantum turbulence in atomic condensates. Such research directions have ...
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.1312737110
更新日期:2014-03-25 00:00:00
abstract::Unconventional myosin 15 is a molecular motor expressed in inner ear hair cells that transports protein cargos within developing mechanosensory stereocilia. Mutations of myosin 15 cause profound hearing loss in humans and mice; however, the properties of this motor and its regulation within the stereocilia organelle 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.1409459111
更新日期:2014-08-26 00:00:00
abstract::GTP hydrolysis by elongation factor Tu (EF-Tu), a translational GTPase that delivers aminoacyl-tRNAs to the ribosome, plays a crucial role in decoding and translational fidelity. The basic reaction mechanism and the way the ribosome contributes to catalysis are a matter of debate. Here we use mutational analysis in co...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2014-10-07 00:00:00
abstract::We have identified an adenovirus type 5(Ad5) early gene function located in early region 1 which is required for the production of early cytoplasmic mRNAs corresponding to early regions 2, 3, and 4. Mutant dl312 (lacks the segment between 1.5 and 4.5 map units) grows as well as wild-type virus in 293 cells (Ad5-trans...
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.76.8.3665
更新日期:1979-08-01 00:00:00