Abstract:
:Integrin alphanubeta3 is found on a subset of tumor blood vessels where it is associated with angiogenesis and malignant tumor growth. We designed an alphanubeta3-targeted nanoparticle (NP) encapsulating the cytotoxic drug doxorubicin (Dox) for targeted drug delivery to the alphanubeta3-expressing tumor vasculature. We observed real-time targeting of this NP to tumor vessels and noted selective apoptosis in regions of the alphanubeta3-expressing tumor vasculature. In clinically relevant pancreatic and renal cell orthotopic models of spontaneous metastasis, targeted delivery of Dox produced an antimetastatic effect. In fact, alphanubeta3-mediated delivery of this drug to the tumor vasculature resulted in a 15-fold increase in antimetastatic activity without producing drug-associated weight loss as observed with systemic administration of the free drug. These findings reveal that NP-based delivery of cytotoxic drugs to the alphanubeta3-positive tumor vasculature represents an approach for treating metastatic disease.
journal_name
Proc Natl Acad Sci U S Aauthors
Murphy EA,Majeti BK,Barnes LA,Makale M,Weis SM,Lutu-Fuga K,Wrasidlo W,Cheresh DAdoi
10.1073/pnas.0803728105subject
Has Abstractpub_date
2008-07-08 00:00:00pages
9343-8issue
27eissn
0027-8424issn
1091-6490pii
0803728105journal_volume
105pub_type
杂志文章abstract::Pbx-regulating protein-1 (Prep1) is a tumor suppressor, whereas myeloid ecotropic viral integration site-1 (Meis1) is an oncogene. We show that, to perform these activities in mouse embryonic fibroblasts, both proteins competitively heterodimerize with pre-B-cell leukemia homeobox-1 (Pbx1). Meis1 alone transforms Prep...
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.1321200111
更新日期:2014-03-11 00:00:00
abstract::Most humans in the United States have been infected with BK virus (BKV), a human papovavirus. Because BKV has oncogenic properties, we have investigated whether it may be a cause of human cancer. Basic principles of tumor virology imply that BKV-induced tumors should contain BKV DNA sequences. Therefore, we assayed (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.75.1.454
更新日期:1978-01-01 00:00:00
abstract::Molecular recognition by proteins is fundamental to molecular biology. Dissection of the thermodynamic energy terms governing protein-ligand interactions has proven difficult, with determination of entropic contributions being particularly elusive. NMR relaxation measurements have suggested that changes in protein con...
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.1621154114
更新日期:2017-06-20 00:00:00
abstract::To study the protein structure-function relationship, we propose a method to efficiently create three-dimensional maps of structure space using a very large dataset of > 30,000 Structural Classification of Proteins (SCOP) domains. In our maps, each domain is represented by a point, and the distance between any two poi...
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.1102727108
更新日期:2011-07-26 00:00:00
abstract::During differentiation of 3T3-L1 preadipocytes into adipocytes, transcription of the C/EBP alpha (CCA-AT/enhancer binding protein alpha) gene is activated. The promoter of the C/EBP alpha gene contains a bipartite cis element with binding sites for C/EBP alpha undifferentiated protein (CUP) and an Sp1-like GT box bind...
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.90.15.7312
更新日期:1993-08-01 00:00:00
abstract::MAC5 is a component of the conserved MOS4-associated complex. It plays critical roles in development and immunity. Here we report that MAC5 is required for microRNA (miRNA) biogenesis. MAC5 interacts with Serrate (SE), which is a core component of the microprocessor that processes primary miRNA transcripts (pri-miRNAs...
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.2008283117
更新日期:2020-09-22 00:00:00
abstract::Myosin I, an actin-dependent force-generating enzyme, has been purified from three mammalian sources: bovine adrenal medulla, adrenal cortex, and brain. The purification procedure includes extraction of tissue with ATP at low ionic strength and coprecipitation with actin, followed by gel filtration on Sepharose 4B, 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.89.2.490
更新日期:1992-01-15 00:00:00
abstract::The archaeological record shows that typically human cultural traits emerged at different times, in different parts of the world, and among different hominin taxa. This pattern suggests that their emergence is the outcome of complex and nonlinear evolutionary trajectories, influenced by environmental, demographic, 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.1620752114
更新日期:2017-07-25 00:00:00
abstract::The molecular mechanisms by which transcription is selectively activated and precisely controlled by signal transducer and activator of transcription (Stat) factors represent a central issue in cytokine-mediated cellular responses. Stat6 mediates responses to IL-4 and antagonizes Stat1 activated by IFN-gamma. We 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.0506981103
更新日期:2006-03-14 00:00:00
abstract::Etioplasts isolated from barley leaves and purified on a Sephadex G-50 (coarse) column were characterized by electron microscopy and nucleic acid analysis. The majority of etioplasts retained an intact outer envelope, and contamination by other fragments was extremely low. The level of gibberellin-like substances extr...
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.73.1.138
更新日期:1976-01-01 00:00:00
abstract::Sinuous patterns traced by fluid flows are a ubiquitous feature of physical landscapes on Earth, Mars, the volcanic floodplains of the Moon and Venus, and other planetary bodies. Typically discussed as a consequence of migration processes in meandering rivers, sinuosity is also expressed in channel types that show lit...
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.1214074110
更新日期:2013-05-21 00:00:00
abstract::The spleen from a patient with adult Gaucher's disease was shown to be deficient in a beta-glucosidase (EC 3.2.1.21) isoenzyme that has optimal activity at pH 4.0-4.3, and is stimulated by 0.02% Triton X-100. A mixture of spleen homogenates from a control and from the patient contained beta-glucosidase activity equiva...
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.68.11.2810
更新日期:1971-11-01 00:00:00
abstract::The number of red blood cells is normally tightly regulated by a classic homeostatic mechanism based on oxygen sensing in the kidney. Decreased oxygen delivery resulting from anemia induces the production of erythropoietin, which increases red cell production and hence oxygen delivery. Investigations of erythropoietin...
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.0508423103
更新日期:2006-01-17 00:00:00
abstract::Protein kinase C (PKC) phosphorylation stimulates the cystic fibrosis transmembrane conductance regulator (CFTR) channel and enhances its activation by protein kinase A (PKA) through mechanisms that remain poorly understood. We have examined the effects of mutating consensus sequences for PKC phosphorylation and repor...
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.0303411101
更新日期:2004-01-06 00:00:00
abstract::Cytochrome c peroxidase reacts with peroxide to form compound I, which contains an oxyferryl heme and an indolyl radical at Trp-191. The indolyl free radical has a half-life of several hours at room temperature, and this remarkable stability is essential for the catalytic function of cytochrome c peroxidase. 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.91.23.11118
更新日期:1994-11-08 00:00:00
abstract::When an unusually high frequency of an allele is encountered in a population, "founder effect" is often invoked as an explanation. As usually used, the term implies the disproportionate increase through chance (rather than selection) of an allele contributed to the population by a particular ancestor. While genetic 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.75.3.1442
更新日期:1978-03-01 00:00:00
abstract::8-Oxoguanine (8OG) is efficiently bypassed by RNA polymerases in vitro and in bacterial cells in vivo, leading to mutant transcripts by directing incorporation of an incorrect nucleotide during transcription. Such transcriptional mutagenesis (TM) may produce a pool of mutant proteins. In contrast, transcription-couple...
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.0806464105
更新日期:2008-12-02 00:00:00
abstract::The apoprotein corresponding to the mammalian photoreceptor rhodopsin has been expressed by using suspension cultures of HEK293S cells in defined media that contained 6-15N-lysine and 2-13C-glycine. Typical yields were 1.5-1.8 mg/liter. Incorporation of 6-15N-lysine was quantitative, whereas that of 2-13C-glycine was ...
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.96.2.487
更新日期:1999-01-19 00:00:00
abstract::Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD) most commonly through loss of protein expression. In a small subpopulation of patients, missense mutations can cause DMD, Becker muscular dystrophy, or X-linked cardiomyopathy. Nearly one-half of disease-causing missense mutations are located 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.1001517107
更新日期:2010-05-25 00:00:00
abstract::A 600-base-pair region essential for ColE1 and pMBl plasmid replication contains two promoters responsible for the synthesis of two RNA molecules central to copy number control. One promoter directs synthesis of the primer RNA precursor. The second promoter directs the synthesis of a small RNA molecule, RNAl, which ac...
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.79.20.6313
更新日期:1982-10-01 00:00:00
abstract::The severe acute respiratory syndrome coronavirus 2 originated in Wuhan, China at the end of 2019 and rapidly spread in more than 100 countries. Researchers in different fields have been working on finding explanations for the unequal impact of the virus and deaths from the associated coronavirus disease 2019 (COVID-1...
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.2008581117
更新日期:2020-08-11 00:00:00
abstract::More than half of all Salmonella enterica serovar Typhi genes still remain unannotated. Although pathogenesis of S. Typhi is incompletely understood, treatment of typhoid fever is complicated by the emergence of drug resistance. Effectiveness of the currently available vaccines is also limited. In search of novel viru...
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.1016180108
更新日期:2011-02-22 00:00:00
abstract::Feedback loops are ubiquitous features of biological networks and can produce significant phenotypic heterogeneity, including a bimodal distribution of gene expression across an isogenic cell population. In this work, a combination of experiments and computational modeling was used to explore the roles of multiple fee...
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.1211902109
更新日期:2012-11-27 00:00:00
abstract::There has been recent experimental support for efficiency wage theories of the labor market. This short paper initiates the larger process of evaluating the boundary conditions of the gift- exchange phenomenon. In particular, we will see whether behavior consistent with the fair wage-effort hypothesis can emerge and 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.152449999
更新日期:2002-10-01 00:00:00
abstract::State transition in photosynthesis is a short-term balancing mechanism of energy distribution between photosystem I (PSI) and photosystem II (PSII). When PSII is preferentially excited (state 2), a pool of mobile light-harvesting complex II (LHCII) antenna proteins is thought to migrate from PSII to PSI, but biochemic...
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.0509952103
更新日期:2006-01-10 00:00:00
abstract::Pancreatic cancer is one of the most deadly cancers affecting the Western world. Because the disease is highly metastatic and difficult to diagnosis until late stages, the 5-y survival rate is around 5%. The identification of molecular cancer drivers is critical for furthering our understanding of the disease and deve...
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.1202490109
更新日期:2012-04-17 00:00:00
abstract::Large mandibular defects are clinically challenging to reconstruct due to the complex anatomy of the jaw and the limited availability of appropriate tissue for repair. We envision leveraging current advances in fabrication and biomaterials to create implantable devices that generate bone within the patients themselves...
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.1819246116
更新日期:2019-04-02 00:00:00
abstract::In the presence of the S polypeptide, maize chloroplast DNA-dependent RNA polymerase preferentially transcribes sequences within the 2200-nucleotide-pair-long maize chloroplast chromosome fragment Eco [unk] from a supercoiled chimeric plasmid cloned in Escherichia coli [Jolly, S. O. & Bogorad, L. (1980) Proc. Natl. Ac...
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.78.6.3423
更新日期:1981-06-01 00:00:00
abstract::Agents that act as anion channel blockers (ACBs) and do not permeate cells appear to inhibit exocytosis in platelets, parathyroid cells, and neutrophils. Based in large part on these observations, anion influx through plasma membrane channels has been considered a factor controlling cellular secretion, but there 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.86.15.5839
更新日期:1989-08-01 00:00:00
abstract::Behavioral and neural evidence reveal a prospective goal-directed decision process that relies on mental simulation of the environment, and a retrospective habitual process that caches returns previously garnered from available choices. Artificial systems combine the two by simulating the environment up to some depth ...
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.1609094113
更新日期:2016-11-08 00:00:00