Abstract:
:Vascular endothelial growth factor receptor-3 (VEGFR-3) is a major mediator of lymphangiogenesis. Recently, VEGFR-3 ligands, VEGF-C, and VEGF-D were reported to promote tumor lymphangiogenesis and lymphatic metastasis, and these processes were inhibited by blocking of the VEGFR-3-signaling pathway. Here, we have adapted the mouse corneal angiogenesis assay to study potential lymphangiogenic factors and inhibitors. Immunohistochemical analysis with lymphatic endothelial markers showed that VEGF-C induces lymphatic as well as blood vessel growth in the cornea. By contrast, VEGF induced angiogenesis but not lymphangiogenesis. Fibroblast growth factor-2 (FGF-2) stimulated both lymphangiogenesis and angiogenesis. FGF-2 up-regulated VEGF-C expression in vascular endothelial and perivascular cells. Furthermore, administration of blocking anti-VEGFR-3 antibodies inhibited the FGF-2-induced lymphangiogenesis. These findings show that VEGFR-3 can mediate lymphangiogenesis induced by other growth factors. Because increased expression of FGF-2 and VEGF-C has been associated with lymphatic metastasis, our results provide a potential strategy for the inhibition of lymphatic metastasis in cancer therapy.
journal_name
Proc Natl Acad Sci U S Aauthors
Kubo H,Cao R,Brakenhielm E,Mäkinen T,Cao Y,Alitalo Kdoi
10.1073/pnas.062040199keywords:
subject
Has Abstractpub_date
2002-06-25 00:00:00pages
8868-73issue
13eissn
0027-8424issn
1091-6490pii
062040199journal_volume
99pub_type
杂志文章abstract::The cellulose synthesizing terminal complex consisting of subunits A, B, C, and D in Acetobacter xylinum spans the outer and inner cell membranes to synthesize and extrude glucan chains, which are assembled into subelementary fibrils and further into a ribbon. We determined the structures of subunit D (AxCeSD/AxBcsD) ...
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.1000601107
更新日期:2010-10-19 00:00:00
abstract::A systematic comparison of crystal structures of nine different B-DNA dodecamers, in three different space groups, with and without A-tracts, shows that crystal packing or lattice forces are of secondary importance for helix axis bending, minor-groove width, and propeller twist. While other local helix parameters may ...
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.91.9.3579
更新日期:1994-04-26 00:00:00
abstract::Cyclonic atmospheric vortices of varying intensity, collectively known as low-pressure systems (LPS), travel northwest across central India and produce more than half of the precipitation received by that fertile region and its ∼600 million inhabitants. Yet, future changes in LPS activity are poorly understood, due 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.1709031115
更新日期:2018-03-13 00:00:00
abstract::The heat shock protein (Hsp)70 family of molecular chaperones interacts with unfolded proteins through a C-terminal substrate-binding domain (SBD) that is controlled by nucleotide binding to the N-terminal domain. The ATPase cycle is regulated by cochaperones, including DnaJ proteins that accelerate ATP hydrolysis to ...
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.0702132105
更新日期:2008-01-29 00:00:00
abstract::Dominantly inherited mutations in the genes encoding presenilins (PS) and the amyloid precursor protein (APP) are the major causes of familial Alzheimer's disease (AD). The prevailing view of AD pathogenesis posits that accumulation of beta-amyloid (Abeta) peptides, particularly Abeta42, is the central event triggerin...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.0608332104
更新日期:2007-01-09 00:00:00
abstract::Using the technique of DNA fingerprinting, we investigated the genetic structure within and among four wild-caught colonies (n = 50 individuals) of a eusocial mammal, the naked mole-rat (Heterocephalus glaber; Rodentia: Bathyergidae). We found that DNA fingerprints of colony-mates were strikingly similar and that betw...
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.87.7.2496
更新日期:1990-04-01 00:00:00
abstract::The Clausius-Mossotti function for the dielectric constant is expanded in terms of single atom and pair polarizabilities, leading to contributions that depend on both the trace and the anisotropy of the pair-polarizability tensor. The short-range contribution of the anisotropic part to the pair polarizabilities has 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.77.6.3098
更新日期:1980-06-01 00:00:00
abstract::In a previous study, we found that human neural stem cells (HNSCs) exposed to high concentrations of secreted amyloid-precursor protein (sAPP) in vitro differentiated into mainly astrocytes, suggesting that pathological alterations in APP processing during neurodegenerative conditions such as Alzheimer's disease (AD) ...
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.0705346104
更新日期:2007-07-24 00:00:00
abstract::The TrkC neurotrophin receptor belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Such a trait has been hypothesized to confer tumor-suppressor activity. Indeed, cells that express these receptors are thought to be dependent on ...
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.1212333110
更新日期:2013-02-19 00:00:00
abstract::The RAD6 gene of Saccharomyces cerevisiae encodes a ubiquitin-conjugating enzyme (E2) that is required for DNA repair, damage-induced mutagenesis, and sporulation. We have cloned the two human RAD6 homologs, designated HHR6A and HHR6B. The two 152-amino acid human proteins share 95% sequence identity with each other 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.88.20.8865
更新日期:1991-10-15 00:00:00
abstract::The atomic displacements associated with the freezing of metals and salts are calculated by treating crystal growth as an assignment problem through the use of an optimal transport algorithm. Converting these displacements into timescales based on the dynamics of the bulk liquid, we show that we can predict the activa...
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.1915806117
更新日期:2020-02-18 00:00:00
abstract::Cysteine site-directed mutagenesis was used to create variants of Escherichia coli ribosomal protein L7/L12 that have single cysteine substitutions, at residues 63 or 89, located in different exposed loops in the structure of the globular C-terminal domain indicated by the crystallographic structure. That structure 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.90.21.9828
更新日期:1993-11-01 00:00:00
abstract::Micrometeorites with diameter approximately 100-200 microm dominate the flux of extraterrestrial matter on Earth. The vast majority of micrometeorites are chemically, mineralogically, and isotopically related to carbonaceous chondrites, which amount to only 2.5% of meteorite falls. Here, we report the discovery of 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.0900328106
更新日期:2009-04-28 00:00:00
abstract::We have shown that 3-nitropropionate, an isoelectronic analogue of succinate, is a suicide inactivator of succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1] as follows. (i) When rat liver mitochondria oxidize succinate in the presence of 3-nitropropionate carbanion, the rate of O(2) consumption...
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.74.9.3767
更新日期:1977-09-01 00:00:00
abstract::Under particular circumstances like lactation and fasting, the blood-borne monocarboxylates acetoacetate, beta-hydroxybutyrate, and lactate represent significant energy substrates for the brain. Their utilization is dependent on a transport system present on both endothelial cells forming the blood-brain barrier and 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.95.7.3990
更新日期:1998-03-31 00:00:00
abstract::The structure of DNA toroids made of individual DNA molecules of various lengths (3,000 to 55,000 bp) was studied, by using partially filled bacteriophage capsids in conjunction with cryoelectron microscopy. The tetravalent cation spermine was diffused through the capsid to condense the DNA under conditions that were ...
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.0901240106
更新日期:2009-06-09 00:00:00
abstract::The origin of vertebrate eyes is still enigmatic. The "frontal eye" of amphioxus, our most primitive chordate relative, has long been recognized as a candidate precursor to the vertebrate eyes. However, the amphioxus frontal eye is composed of simple ciliated cells, unlike vertebrate rods and cones, which display more...
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.1207580109
更新日期:2012-09-18 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.1809707115
更新日期:2019-01-02 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.1600965113
更新日期:2016-08-02 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.95.7.3931
更新日期:1998-03-31 00:00:00
abstract::Mannose-labeled glycopeptides from the surface of growing and nongrowing human diploid cells (KL-2) were separated into neutral glycopeptides and acidic glycopeptides by paper electrophoresis. Growth-dependent alterations occurred in oligomannosyl cores in the neutral glycopeptides; namely, the neutral glycopeptides 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.72.8.3139
更新日期:1975-08-01 00:00:00
abstract::Most current diagnostic tests for tuberculosis do not reveal the species or strain of pathogen causing pulmonary infection, which can lead to inappropriate treatment regimens and the spread of disease. Here, we report an assay for mycobacterial strain assignment based on genetically conserved mycobacterial sulfatases....
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.1222041110
更新日期:2013-08-06 00:00:00
abstract::Elevated eukaryotic initiation factor 4E (eIF4E) levels frequently occur in a variety of human cancers. Overexpression of eIF4E promotes cellular transformation by selectively increasing the translation of proliferative and prosurvival mRNAs. These mRNAs possess highly structured 5'-UTRs that impede ribosome recruitme...
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.1303781110
更新日期:2013-08-13 00:00:00
abstract::A defect in the yeast GEF1 gene, a CLC chloride channel homolog leads to an iron requirement and cation sensitivity. The iron requirement is due to a failure to load Cu2+ onto a component of the iron uptake system, Fet3. This process, which requires both Gef1 and the Menkes disease Cu2+-ATPase yeast homolog Ccc2, occu...
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.95.7.4046
更新日期:1998-03-31 00:00:00
abstract::Two RNA fractions have been isolated and purified from both oncogenic and nononcogenic strains of Agrobacterium tumefaciens. Both RNAs are capable of inducing the formation of transplantable tumors when introduced at wound sites in stems of Datura stramonium plants. One of these RNA fractions was found to be bound to ...
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.71.5.1585
更新日期:1974-05-01 00:00:00
abstract::Ten eleven translocation (TET) enzymes (TET1/TET2/TET3) and thymine DNA glycosylase (TDG) play crucial roles in early embryonic and germ cell development by mediating DNA demethylation. However, the molecular mechanisms that regulate TETs/TDG expression and their role in cellular differentiation, including that of 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.1317397110
更新日期:2013-10-29 00:00:00
abstract::Hybridoma technology was used for preparation of murine monoclonal antibodies of high titer against bone-Gla protein and osteonectin. A procedure of immunization and hybridization similar to that already described [Katzmann, J.A., Nesheim, M.E., Hibbard, L.S. & Mann, K.G. (1981) Proc. Natl. Acad. Sci. USA 78, 162-166;...
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.81.9.2868
更新日期:1984-05-01 00:00:00
abstract::The wide diversity of dendritic trees is one of the most striking features of neural circuits. Here we develop a general quantitative theory relating the total length of dendritic wiring to the number of branch points and synapses. We show that optimal wiring predicts a 2/3 power law between these measures. We demonst...
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.1200430109
更新日期:2012-07-03 00:00:00
abstract::In 2005 four outstanding multiple burials were discovered near Eulau, Germany. The 4,600-year-old graves contained groups of adults and children buried facing each other. Skeletal and artifactual evidence and the simultaneous interment of the individuals suggest the supposed families fell victim to a violent event. In...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.0807592105
更新日期:2008-11-25 00:00:00
abstract::The ability of beta cells to endure assaults may be relevant in the development of insulin-dependent diabetes mellitus. This study examines the susceptibility of human pancreatic islets to agents that are cytotoxic for rodent beta cells--i.e., sodium nitroprusside (NP, a nitric oxide donor), streptozotocin (SZ), or al...
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.91.20.9253
更新日期:1994-09-27 00:00:00