Abstract:
:The secreted Bv8 protein has been recently characterized as a regulator of myeloid cell mobilization and a neutrophil-derived mediator of tumor angiogenesis in several xenografts, but its role in tumor progression in an endogenous setting was unknown. The rat insulin promoter (RIP)-T-antigen (Tag) is a well characterized transgenic mouse model of multistage pancreatic beta-cell tumorigenesis. Also, the role of neutrophils in RIP-Tag angiogenic switching, as assessed by systemic ablation using anti-Gr1 antibodies at different stages of tumor progression, has been recently described. Here, we show that early treatment of RIP-Tag mice with anti-Bv8 antibodies resulted in a significant reduction in the number of angiogenic islets relative to control antibody-treated mice, implicating Bv8 in the angiogenic switch during neoplasia. Histological analysis showed a significant reduction in vascular surface areas in hyperplastic and angiogenic lesions in pancreatic islets from anti-Bv8-treated mice. Anti-Bv8 treatment also inhibited the mobilization and homing of CD11b+Gr1+ cells to the peripheral blood and the emerging neoplastic lesions. However, anti-Bv8 treatment had no effect on tumor vascularization or burden when initiated at later stages of tumor progression. The stage-dependent efficacy of anti-Bv8 treatment appears remarkably similar to that reported after neutrophil ablation, suggesting that Bv8 is an important mediator of neutrophil-dependent angiogenesis in this transgenic model. In summary, our studies verify a role for Bv8 in the mobilization and recruitment of myeloid cells and in the induction of tumor angiogenesis in the early stages of neoplastic progression.
journal_name
Proc Natl Acad Sci U S Aauthors
Shojaei F,Singh M,Thompson JD,Ferrara Ndoi
10.1073/pnas.0712185105subject
Has Abstractpub_date
2008-02-19 00:00:00pages
2640-5issue
7eissn
0027-8424issn
1091-6490pii
0712185105journal_volume
105pub_type
杂志文章abstract::We consider the sequential estimation of p, the probability of success in an infinite sequence of Bernoulli trials, when the loss incurred in stopping after n trials and estimating p by some function delta(n) of the first n outcomes is taken to be [Formula: see text] The loss due to error of estimation is thus the sym...
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.72.1.191
更新日期:1975-01-01 00:00:00
abstract::Biomass burning drives changes in greenhouse gases, climate-forcing aerosols, and global atmospheric chemistry. There is controversy about the magnitude and timing of changes in biomass burning emissions on millennial time scales from preindustrial to present and about the relative importance of climate change and hum...
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.1807172115
更新日期:2018-12-04 00:00:00
abstract::Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common extranodal lymphoid cell neoplasia; it frequently follows chronic bacteria-induced inflammation in various tissues. MALT lymphomas are characterized genetically by the t(11;18)(q21;q21) translocation, which yields chimeric transcripts encoding struct...
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.0402415101
更新日期:2004-06-15 00:00:00
abstract::Chronic microbial infections are associated with fibrotic and inflammatory reactions known as granulomas showing similarities to wound-healing and tissue repair processes. We have previously mapped three leishmaniasis susceptibility loci, designated lmr1, -2, and -3, which exert their effect independently of T cell im...
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.0505630102
更新日期:2005-10-25 00:00:00
abstract::Activation of JAK2 by chromosomal translocation or point mutation is a recurrent event in hematopoietic malignancies, including acute leukemias and myeloproliferative disorders. Although the effects of activated JAK2 signaling have been examined in cell lines and murine models, the functional consequences of deregulat...
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.0604902103
更新日期:2006-11-07 00:00:00
abstract::We report on the production of tumor necrosis factor (TNF)-alpha and TNF-beta by mitogen-activated peripheral blood lymphocytes or enriched monocyte subpopulations from human leukocyte antigen (HLA)-typed healthy subjects. The results indicate that HLA-DR2- and DQw1-positive donors frequently exhibit low production of...
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.87.3.1233
更新日期:1990-02-01 00:00:00
abstract::Rapamycin is a potent immunosuppressant that blocks the G1/S transition in antigen-activated T cells and in yeast. The similar effects of rapamycin in animal cells and yeast suggest that the biochemical steps affected by rapamycin are conserved. Using a two-hybrid system we isolated mammalian clones that interact 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.91.26.12574
更新日期:1994-12-20 00:00:00
abstract::C.B-17 severe combined immunodeficient (scid) mice carry the scid mutation and are severely deficient in both T cell- and B cell-mediated immunity, apparently as a result of defective V(D)J joining of the immunoglobulin and T-cell receptor gene elements. In the present studies, we have defined the tissue, cellular, an...
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.88.4.1394
更新日期:1991-02-15 00:00:00
abstract::Glands of the uterus are essential for pregnancy establishment. Forkhead box A2 (FOXA2) is expressed specifically in the glands of the uterus and a critical regulator of glandular epithelium (GE) differentiation, development, and function. Mice with a conditional deletion of FOXA2 in the adult uterus, created using 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.2014272117
更新日期:2020-09-22 00:00:00
abstract::Often, resistance to drugs is an obstacle to a successful treatment of cancer. In spite of the importance of the problem, the actual mechanisms that control the evolution of drug resistance are not fully understood. Many attempts to study drug resistance have been made in the mathematical modeling literature. Clearly,...
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.1007726107
更新日期:2010-09-28 00:00:00
abstract::Nitric oxide (NO) mediates several biological actions, including relaxation of blood vessels, cytotoxicity of activated macrophages, and formation of cGMP by activation of glutamate receptors in cerebellar slices. Nitric oxide synthase (EC 1.14.23.-) immunoreactivity is colocalized with nicotinamide adenine di-nucleot...
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.88.14.6368
更新日期:1991-07-15 00:00:00
abstract::Island biogeography theory posits that species richness increases with island size and decreases with isolation. This logic underpins much conservation policy and regulation, with preference given to conserving large, highly connected areas, and relative ambivalence shown toward protecting small, isolated habitat patc...
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.1813051115
更新日期:2019-01-15 00:00:00
abstract::Lipoxin B (LXB) was prepared by incubation of (15S)-15-hydroperoxy-5,8,11-cis-13-trans-icosatetraenoic acid (15-HPETE) with human leukocytes. Comparison with a number of trihydroxyicosatetraenes prepared by total synthesis showed that biologically derived LXB is (5S,14R,15S)-5,14,15-trihydroxy-6,10,12-trans-8-cis-icos...
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.83.7.1983
更新日期:1986-04-01 00:00:00
abstract::Knowing how motile bacteria move near and along a solid surface is crucial to understanding such diverse phenomena as the migration of infectious bacteria along a catheter, biofilm growth, and the movement of bacteria through the pore spaces of saturated soil, a critical step in the in situ bioremediation of contamina...
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.92.13.6195
更新日期:1995-06-20 00:00:00
abstract::Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are prototypic growth factors and receptor tyrosine kinases which have critical functions in development. We show that PDGFs share a conserved region in their prodomain sequences which can remain noncovalently associated with the mature cystine-knot ...
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.1000806107
更新日期:2010-06-22 00:00:00
abstract::The explosive growth in citizen science combined with a recalcitrance on the part of mainstream science to fully embrace this data collection technique demands a rigorous examination of the factors influencing data quality and project efficacy. Patterns of contributor effort and task performance have been well reviewe...
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.1807186115
更新日期:2019-02-05 00:00:00
abstract::Total chemical synthesis was used to prepare the mirror image (D-protein) form of the angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against D-VEGF-A was used to screen designed libraries based on a unique small protein scaffold in order to identify a high affinity ligand. Chemically syn...
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.1210483109
更新日期:2012-09-11 00:00:00
abstract::Protein tyrosine phosphorylation in purified synaptic vesicles from rat forebrain has been studied in the presence of Mn2+ and orthovanadate. High levels of endogenous protein tyrosine phosphorylation were observed. Four major phosphoproteins, with apparent molecular masses of 105, 94, 38, and 30 kDa, were shown to co...
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.85.3.762
更新日期:1988-02-01 00:00:00
abstract::A central question in protein-DNA recognition is the origin of the specificity that permits binding to the correct site in the presence of excess, nonspecific DNA. In the P22 Arc repressor, the Phe-10 side chain is part of the hydrophobic core of the free protein but rotates out to pack against the sugar-phosphate bac...
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.96.3.811
更新日期:1999-02-02 00:00:00
abstract::The Hyal-1 locus, which we have previously described and mapped to mouse chromosome 9, influences the serum levels and molecular weight forms of hyaluronidase. We have also shown that the growth of two transplantable tumors, the 3LL carcinoma and the B16F10 melanoma, is influenced by the alleles at Hyal-1, in that 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.90.12.5708
更新日期:1993-06-15 00:00:00
abstract::Huntington disease stems from a mutation of the protein huntingtin and is characterized by selective loss of discrete neuronal populations in the brain. Despite a massive loss of neurons in the corpus striatum, NO-generating neurons are intact. We recently identified a brain-specific protein that associates with hunti...
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.93.10.4839
更新日期:1996-05-14 00:00:00
abstract::Three-dimensional microfluidic systems were fabricated and used to pattern proteins and mammalian cells on a planar substrate. The three-dimensional topology of the microfluidic network in the stamp makes this technique a versatile one with which to pattern multiple types of proteins and cells in complex, discontinuou...
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.040562297
更新日期:2000-03-14 00:00:00
abstract::The molecular mechanism of growth hormone release by synthetic somatocrinin was investigated on purified hog anterior pituitary secretory granules; the granules were found to contain a cAMP-dependent protein kinase that catalyzed [gamma-32P]-ATP histone phosphorylation with maximal rates ranging from 1 to 5 nmol of Pi...
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.80.21.6538
更新日期:1983-11-01 00:00:00
abstract::IL-7 and thymic stromal lymphopoietin (TSLP) are two major cytokines controlling murine B cell development. IL-7 has been studied extensively, but only recently has it become possible to unravel the role of TSLP in detail. We studied the biological activities of TSLP in B cell development at distinct ages in the mouse...
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.0402919101
更新日期:2004-07-27 00:00:00
abstract::We studied intracellular pH (pHi) regulation in the absence of HCO3- in single mesangial cells (MCs) with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(and -6)carboxyfluorescein. Our approach was to acid load the cells by an NH+4 prepulse and to monitor the subsequent pHi recovery. Previous work on MCs and other ce...
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.87.15.5921
更新日期:1990-08-01 00:00:00
abstract::Cerebellar granule cells grown in the presence of a serum complex differentiate but are resistant to the lethal action of excitatory amino acids. When these cells are grown also in the presence of insulin-like growth factor I (IGF-I) they become fully susceptible to the toxic, lethal action of glutamate. The glutamate...
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.90.18.8752
更新日期:1993-09-15 00:00:00
abstract::Of all the myosin filaments in muscle, the most important in terms of human health, and so far the least studied, are those in the human heart. Here we report a 3D single-particle analysis of electron micrograph images of negatively stained myosin filaments isolated from human cardiac muscle in the normal (undiseased)...
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.1212708110
更新日期:2013-01-02 00:00:00
abstract::A mol of creatine kinase (EC 2.7.3.2), an enzyme with two identical subunits can be titrated very rapidly and stoichiometrically with 2 mol of 2-chloromercuri-4-nitrophenol, an environmentally sensitive chromophoric probe specific for thiols. Chemical modification does not inactivate the enzyme nor can the reaction be...
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.70.10.2858
更新日期:1973-10-01 00:00:00
abstract::Yawn contagion in humans has been proposed to be related to our capacity for empathy. It is presently unclear whether this capacity is uniquely human or shared with other primates, especially monkeys. Here, we show that in gelada baboons (Theropithecus gelada) yawning is contagious between individuals, especially thos...
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.0910891106
更新日期:2009-11-17 00:00:00
abstract::The temperature dependence of migration rate and of the thermotactic sensitivity of pseudoplasmodia of Dictyostelium discoideum has been measured. Migration rate increases with temperature to 20 degrees, is temperature insensitive from 20 degrees to 27.5 degrees, and decreases with temperature to 29 degrees, above whi...
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.74.5.2007
更新日期:1977-05-01 00:00:00