Abstract:
:Experimental in vivo tumor models are essential for comprehending the dynamic process of human cancer progression, identifying therapeutic targets, and evaluating antitumor drugs. However, current rodent models are limited by high costs, long experimental duration, variability, restricted accessibility to the tumor, and major ethical concerns. To avoid these shortcomings, we investigated whether tumor growth on the chick chorio-allantoic membrane after human glioblastoma cell grafting would replicate characteristics of the human disease. Avascular tumors consistently formed within 2 days, then progressed through vascular endothelial growth factor receptor 2-dependent angiogenesis, associated with hemorrhage, necrosis, and peritumoral edema. Blocking of vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor signaling pathways by using small-molecule receptor tyrosine kinase inhibitors abrogated tumor development. Gene regulation during the angiogenic switch was analyzed by oligonucleotide microarrays. Defined sample selection for gene profiling permitted identification of regulated genes whose functions are associated mainly with tumor vascularization and growth. Furthermore, expression of known tumor progression genes identified in the screen (IL-6 and cysteine-rich angiogenic inducer 61) as well as potential regulators (lumican and F-box-only 6) follow similar patterns in patient glioma. The model reliably simulates key features of human glioma growth in a few days and thus could considerably increase the speed and efficacy of research on human tumor progression and preclinical drug screening.
journal_name
Proc Natl Acad Sci U S Aauthors
Hagedorn M,Javerzat S,Gilges D,Meyre A,de Lafarge B,Eichmann A,Bikfalvi Adoi
10.1073/pnas.0408622102keywords:
subject
Has Abstractpub_date
2005-02-01 00:00:00pages
1643-8issue
5eissn
0027-8424issn
1091-6490pii
0408622102journal_volume
102pub_type
杂志文章abstract::High molecular weight polypeptides (HMWPs) of 270,000 to 340,000 were found to be major components of intermediate filaments prepared by Triton X-100 extraction after spreading of rat glioma C6, HeLa, Chinese hamster ovary, and simian virus 40-transformed Chinese hamster lung cells. C6 HMWPs were shown to resemble hig...
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.77.8.4808
更新日期:1980-08-01 00:00:00
abstract::Replacing Leu-182 by Ala in yeast alcohol dehydrogenase (YADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) yields a mutant that retains 34% of its kcat value and makes one stereochemical "mistake" every 850,000 turnovers (instead of approximately 1 error every 7,000,000,000 turnovers in native YADH) in its selection of t...
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.88.19.8420
更新日期:1991-10-01 00:00:00
abstract::Gastrulation is a fundamental process in early development that results in the formation of three primary germ layers. During avian gastrulation, presumptive mesodermal cells in the dorsal epiblast ingress through a furrow called the primitive streak (PS), and subsequently move away from the PS and form adult tissues....
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.0606100103
更新日期:2006-12-26 00:00:00
abstract::Arginine is an amino acid that serves as a substrate for nitric oxide synthase and arginase. As such, arginine has the potential to influence diverse fundamental processes in the lung. Here we report that the arginine transport protein, cationic amino acid transporter (CAT)2, has a critical role in regulating lung inf...
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.0605478103
更新日期:2006-10-03 00:00:00
abstract::Larval fishes suffer prodigious mortality rates, eliminating 99% of the brood within a few days after first feeding. Hjort (1914) famously attributed this "critical period" of low survival to the larvae's inability to obtain sufficient food [Hjort (1914) Rapp P-v Réun Cons Int Explor Mer 20:1-228]. However, the cause ...
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.1323205111
更新日期:2014-06-03 00:00:00
abstract::Despite the widespread use of silicon in modern technology, its peculiar thermal expansion is not well understood. Adapting harmonic phonons to the specific volume at temperature, the quasiharmonic approximation, has become accepted for simulating the thermal expansion, but has given ambiguous interpretations for micr...
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.1707745115
更新日期:2018-02-27 00:00:00
abstract::A 32-base-pair (bp) DNA duplex with deletions in one strand, and thus extra bases in the opposing strand, was ligated head-to-tail to produce linear and circular multimers. The electrophoretic mobility of the linear multimers was analyzed in polyacrylamide gels and the size of the circular DNA was determined by electr...
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.86.13.4833
更新日期:1989-07-01 00:00:00
abstract::In MtrF, an outer-membrane multiheme cytochrome, the 10 heme groups are arranged in heme binding domains II and IV along the pseudo-C2 axis, forming the electron transfer (ET) pathways. Previous reports based on molecular dynamics simulations showed that the redox potential (Em) values for the heme pairs located in sy...
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.1617615114
更新日期:2017-03-14 00:00:00
abstract::The human amygdala plays a key role in recognizing facial emotions and neurons in the monkey and human amygdala respond to the emotional expression of faces. However, it remains unknown whether these responses are driven primarily by properties of the stimulus or by the perceptual judgments of the perceiver. We invest...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 临床试验,杂志文章
doi:10.1073/pnas.1323342111
更新日期:2014-07-29 00:00:00
abstract::Amyloid beta (Aβ) is a major pathological marker in Alzheimer's disease (AD), which is principally regulated by the rate-limiting β-secretase (i.e., BACE1) cleavage of amyloid precursor protein (APP). However, how BACE1 activity is posttranslationally regulated remains incompletely understood. Here, we show that BACE1...
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.1800498115
更新日期:2018-04-10 00:00:00
abstract::Cosuppression results in the degradation of RNA from host genes and homologous transgenes after transcription in the nucleus. By using grafting experiments, we have shown previously that a systemic signal mediates the propagation of cosuppression of Nia host genes and 35S-Nia2 transgenes from silenced 35S-Nia2 transge...
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.95.16.9675
更新日期:1998-08-04 00:00:00
abstract::Peptidoglycan recognition proteins (PGRPs) are highly conserved pattern-recognition molecules of the innate immune system that bind bacterial peptidoglycans (PGNs), which are polymers of alternating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) cross-linked by short peptide stems. Human PRGPs are bactericid...
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.0701453104
更新日期:2007-05-22 00:00:00
abstract::Go is a specific class ("other") of signal-transducing heterotrimeric GTP-binding proteins (G proteins) that is expressed in high levels in mammalian brain. We have cloned two different rat cDNAs encoding the alpha subunit of Go (Go alpha-1 and Go alpha-2) and a human Go alpha chromosomal gene. The human Go alpha gene...
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.88.8.2974
更新日期:1991-04-15 00:00:00
abstract::We have detected a proteolytic mechanism in chloroplasts that selectively and rapidly degrades the imported small subunit of ribulose 1,5-bisphosphate carboxylase when pools of the chloroplast-synthesized large subunit are depleted. This degradation system is constitutively present and appears to be responsible for pr...
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.80.9.2632
更新日期:1983-05-01 00:00:00
abstract::The U.S. case against Iran is based on Iran's deceptions regarding nuclear weapons development. This case is buttressed by assertions that a state so petroleum-rich cannot need nuclear power to preserve exports, as Iran claims. The U.S. infers, therefore, that Iran's entire nuclear technology program must pertain to w...
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.0603903104
更新日期:2007-01-02 00:00:00
abstract::p70 S6 kinase (p70(S6k)) is a mitogen-activated protein kinase that plays a central role in the control of mRNA translation. It physiologically phosphorylates the S6 protein of the 40s ribosomal subunit in response to mitogenic stimuli and is a downstream component of the rapamycin-sensitive pathway, which includes 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.95.14.8351
更新日期:1998-07-07 00:00:00
abstract::In this study we report the X-ray crystal structure of the extracellular domain (ECD) of the human neuronal α2 nicotinic acetylcholine receptor (nAChR) subunit in complex with the agonist epibatidine at 3.2 Å. Interestingly, α2 was crystallized as a pentamer, revealing the intersubunit interactions in a wild type neur...
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.1602619113
更新日期:2016-08-23 00:00:00
abstract::Large-scale analysis of the GC-content distribution at the gene level reveals both common features and basic differences in genomes of different groups of species. Sharp changes in GC content are detected at the transcription boundaries for all species analyzed, including human, mouse, rat, chicken, fruit fly, and wor...
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.0407821101
更新日期:2004-11-30 00:00:00
abstract::The modern Old World Monkeys (Superfamily Cercopithecoidea, Family Cercopithecidae) can be traced back into the late Miocene, but their origin and subsequent diversification is obscured by the scarcity of terrestrial fossil sites in Africa between 15 and 6 Ma. Here, we document the presence of cercopithecids at 12.5 M...
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.1213691110
更新日期:2013-04-09 00:00:00
abstract::The phosphorylation state of the Na,K-ATPase alpha subunit has been examined in 32P-labeled sciatic nerves of control and streptozotocin-treated diabetic rats. Intact nerves were challenged with protein kinase (PK) modulators and alpha-subunit 32P labeling was analyzed after immunoprecipitation. In control nerves, the...
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.91.13.6211
更新日期:1994-06-21 00:00:00
abstract::To assess the contribution to immunoglobulin heavy chain diversity made by recombination between variable region (VH) genes and joining region (JH) genes, we have determined the sequence of about 2000 nucleotides spanning the rearranged JH gene cluster associated with the VH gene expressed in plasmacytoma HPC76. The 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.78.1.509
更新日期:1981-01-01 00:00:00
abstract::Observations from human microbiome studies are often conflicting or inconclusive. Many factors likely contribute to these issues including small cohort sizes, sample collection, and handling and processing differences. The field of microbiome research is moving from 16S rDNA gene sequencing to a more comprehensive gen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.1519288112
更新日期:2015-11-10 00:00:00
abstract::ErbB3 (HER3) is a member of the EGF receptor (EGFR) family of receptor tyrosine kinases, which, unlike the other three family members, contains a pseudo kinase in place of a tyrosine kinase domain. In cancer, ErbB3 activation is driven by a ligand-dependent mechanism through the formation of heterodimers with EGFR, Er...
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.1518361112
更新日期:2015-10-27 00:00:00
abstract::Folding mechanisms of proteins incorporated within supramolecular assemblies, including viruses, are little understood and may differ fundamentally from folding mechanisms of small globular proteins. We describe a novel Raman dynamic probe of hydrogen-isotope exchange to investigate directly these protein folding/asse...
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.95.17.9885
更新日期:1998-08-18 00:00:00
abstract::Three allelic variants of P-pilus-associated G-adhesins (lectins) with different cell-binding properties were recently described. Here we have analyzed Escherichia coli HB101 strains expressing the recombinant G-adhesin variants for their ability to agglutinate erythrocytes from various species as this relates to the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.88.20.9340
更新日期:1991-10-15 00:00:00
abstract::Brn-4 is a member of the POU transcription factor family and is expressed in the central nervous system. In this study, we addressed whether Brn-4 regulates expression of the D1A dopamine receptor gene. We found a functional Brn-4 responsive element in the intron of this gene by means of cotransfection chloramphenical...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.93.21.11933
更新日期:1996-10-15 00:00:00
abstract::Fusions of the lac operon to genes induced by treatment with sublethal levels of alkylating agents have been selected from random insertions of the Mu-dl(ApRlac) phage by screening for induction of beta-galactosidase activity in the presence of methyl methanesulfonate. Genetic analysis reveals that these fusions resul...
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.81.13.4110
更新日期:1984-07-01 00:00:00
abstract::Uncoupling protein 1 (UCP1) catalyzes fatty acid-activated, purine nucleotide-sensitive proton leak across the mitochondrial inner membrane of brown adipose tissue to produce heat, and could help combat obesity and metabolic disease in humans. Studies over the last 30 years conclude that the protein is a dimer, bindin...
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.1503833112
更新日期:2015-06-02 00:00:00
abstract::Anatoxin-a, a bicyclic amine isolated from blue-green alga, binds to the nicotinic acetylcholine receptor of Torpedo electric tissue, thereby inducing conformational changes in the postsynaptic receptor--ion channel complex as evidenced by alterations in the binding of radiolabeled ligands to the complex. Anatoxin-a b...
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.78.7.4639
更新日期:1981-07-01 00:00:00
abstract::Gastrointestinal stromal tumor (GIST) has emerged as a clinically distinct type of sarcoma with frequent overexpression and mutation of the c-Kit oncogene and a favorable response to imatinib mesylate [also known as STI571 (Gleevec)] therapy. However, a significant diagnostic challenge remains in the differentiation o...
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.0611373104
更新日期:2007-02-27 00:00:00