Abstract:
:Blockage of Delta-like 4 (DLL4)-directed Notch signaling induces excessive tip cell formation and endothelial proliferation resulting in dysfunctional angiogenesis in tumors. MMGZ01, as a murine anti-human DLL4 monoclonal antibody, specifically binds to human DLL4 and blocks Notch pathway. Here, the structure of MMGZ01 variable fragment (Fv) was established and framework region (FR) residues which supported complementarily determining region (CDR) loop conformation were identified. Important residues interactions were also identified through docking MMGZ01 Fv with antigen epitope in DLL4. To humanize the murine antibody, we modified MMGZ01 Fv through CDR grafting and the reconstructed antibody (H3L2) maintained similar structure and binding affinity to parental MMGZ01 after back mutation of 12 canonical murine residues in the FRs. Meanwhile, H3L2 promoted human umbilical vein endothelial cell (HUVEC) proliferation through inhibiting DLL4-directed Notch pathway. Moreover, in MDA-MB-231-bearing nude mice, H3L2 induced dysfunctional angiogenesis and tumor cell apoptosis and showed superior anti-tumor activity. In conclusion, H3L2 is an ideal humanized antibody that inhibits tumor growth through targeting DLL4-Notch pathway and has attracting potentials for clinical applications.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Jia X,Wang W,Xu Z,Wang S,Wang T,Wang M,Wu Mdoi
10.1038/srep27985subject
Has Abstractpub_date
2016-06-15 00:00:00pages
27985issn
2045-2322pii
srep27985journal_volume
6pub_type
杂志文章abstract::To investigate the influence of various factors on the two outcome parameters "procedure - specific complication" (femoral head necrosis, infection, nonunion, femoral neck shortening, screw loosening, implant penetration) and "functional outcome" in patients with displaced and undisplaced femoral neck fracture treated...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-57696-2
更新日期:2020-01-20 00:00:00
abstract::Changes of intracellular and extracellular pH are involved in a variety of physiological and pathological processes, in which regulation of the Ca(2+) release activated Ca(2+) channel (I CRAC) by pH has been implicated. Ca(2+) entry mediated by I CRAC has been shown to be regulated by acidic or alkaline pH. Whereas se...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep16747
更新日期:2015-11-18 00:00:00
abstract::Viewing facial expressions often evokes facial responses in the observer. These spontaneous facial reactions (SFRs) are believed to play an important role for social interactions. However, their developmental trajectory and the underlying neurocognitive mechanisms are still little understood. In the current study, 4- ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-17556-y
更新日期:2017-12-13 00:00:00
abstract::Pancreatic cancer is predominantly lethal, and is primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents, since HDAC plays an important role in cancer initi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep41615
更新日期:2017-01-30 00:00:00
abstract::Papillary thyroid carcinoma (PTC) displays strong but so far largely uncharacterized heritability. Here we studied genetic predisposition in a family with six affected individuals. We genotyped all available family members and conducted whole exome sequencing of blood DNA from two affected individuals. Haplotype analy...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep10566
更新日期:2015-07-02 00:00:00
abstract::Viral oncoproteins E6/E7 play key oncogenic role in human papillomavirus (HPV)-mediated cervical carcinogenesis in conjunction with aberrant activation of cellular signaling events. GLI-signaling has been implicated in metastasis and tumor recurrence of cervical cancer. However, the interaction of GLI-signaling with H...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep34377
更新日期:2016-09-28 00:00:00
abstract::The occurrence of toxic metals in the aquatic environment is as caused by a variety of contaminations which makes difficulty in the concentration prediction. In this study, conventional methods of back-propagation neural network (BPNN) and nonlinear autoregressive network with exogenous inputs (NARX) were applied as b...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-70438-8
更新日期:2020-08-10 00:00:00
abstract::Individuals with Angelman syndrome (AS) are characterized by severe cognitive impairments alongside an enhanced drive for social engagement. As knowledge on imitation skills in this population is limited, we conducted the first controlled study of imitation in AS. We examined how 23 individuals with AS and 21 typicall...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-72079-3
更新日期:2020-10-02 00:00:00
abstract::Most large carnivore populations currently occur in heterogeneous landscapes, with source populations embedded in a matrix of human-dominated habitats. Understanding changes in distribution of endangered carnivores is critical for prioritizing and implementing conservation strategies. We examined distribution and dyna...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-39293-0
更新日期:2019-02-28 00:00:00
abstract::We investigate the role of the spatial evolution of the acoustic field in stimulated Brillouin scattering processes in short high-gain structures. When the gain is strong enough that the gain length becomes comparable to the acoustic wave decay length of order 100 microns, standard approximations treating the acoustic...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep13656
更新日期:2015-09-04 00:00:00
abstract::The aggregation of gold nanoparticles (AuNPs) is known to induce an enhancement of localized surface plasmon resonance due to the coupling of plasmonic fields of adjacent nanoparticles. Here we show that AuNPs aggregation also causes a significant enhancement of chemiluminescence in the presence of luminophores. The p...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-14580-w
更新日期:2017-10-25 00:00:00
abstract::Recurrent genetic mutations occur in acute myeloid leukemia (AML) and have been incorporated into risk stratification to predict the prognoses of AML patients. The bone marrow microenvironment plays a critical role in the development and progression of AML. However, the characteristics of the genetic mutation-associat...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-76048-8
更新日期:2020-11-04 00:00:00
abstract::Solid-state femtosecond lasers have stimulated the broad adoption of multiphoton microscopy in the modern laboratory. However, these devices remain costly. Fiber lasers offer promise as a means to inexpensively produce ultrashort pulses of light suitable for nonlinear microscopy in compact, robust and portable devices...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-40871-5
更新日期:2019-03-12 00:00:00
abstract::Many species can successfully colonize new areas despite their propagules having low genetic variation. We assessed whether the decreased genetic diversity could result in temporal fluctuations of genetic parameters of the new populations of an invasive species, western flower thrips, Frankliniella occidentalis, using...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep11877
更新日期:2015-07-03 00:00:00
abstract::Neurite growth is controlled by a complex molecular signaling network that regulates filamentous actin (F-actin) dynamics at the growth cone. The evolutionarily conserved ezrin, radixin, and moesin family of proteins tether F-actin to the cell membrane when phosphorylated at a conserved threonine residue and modulate ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-20755-w
更新日期:2018-02-07 00:00:00
abstract::To pattern electrical metal contacts, electron beam lithography or photolithography are commonly utilized, and these processes require polymer resists with solvents. During the patterning process the graphene surface is exposed to chemicals, and the residue on the graphene surface was unable to be completely removed b...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep25050
更新日期:2016-05-12 00:00:00
abstract::West Nile virus (WNV) is a neurotropic pathogen which causes zoonotic disease in humans. Recently, there have been an increasing number of infected cases and there are no clinically approved vaccines or effective drugs to treat WNV infections in humans. The purpose of this study was to facilitate vaccine and antiviral...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-03670-4
更新日期:2017-06-12 00:00:00
abstract::Determining oil migration distances from source rocks to reservoirs can greatly help in the search for new petroleum accumulations. Concentrations and ratios of polar organic compounds are known to change due to preferential sorption of these compounds in migrating oils onto immobile mineral surfaces. However, these c...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep02487
更新日期:2013-01-01 00:00:00
abstract::The trade of bumble bees started in the early nineties for pollinator-dependent greenhouse plants. Nowadays, its rearing and transport have received public attention, since managed bees can transfer pathogens to wild bee populations. Therefore, guaranteeing pathogen-free bumble bees is fundamental. The major protein s...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-40804-2
更新日期:2019-03-12 00:00:00
abstract::Fat character is an important index in duck culture that linked to local flavor, feed cost and fat intake for costumers. Since the regulation networks in duck lipid metabolism had not been reported very clearly, we aimed to explore the potential miRNA-mRNA pairs and their regulatory roles in duck lipid metabolism. Her...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep27418
更新日期:2016-06-08 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-020-64341-5
更新日期:2020-04-29 00:00:00
abstract::We developed an optimized Dipheylthiocarbazone or Dithizone (DTZ) with improved physical and chemical properties to characterize human islets and insulin-producing cells differentiated from embryonic stem cells. Application of the newly formulated iDTZ (i stands for islet) over a range of temperatures, time intervals ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-45678-y
更新日期:2019-06-26 00:00:00
abstract::Conventional crystalline β-MnO2 usually exhibits poor electrochemical activities due to the narrow tunnels in its rutile-type structure. In this study, we synthesized a novel 2D β-MnO2 network with long-range order assembled by β-MnO2 nanowires and demonstrated that the novel 2D β-MnO2 network exhibits enhanced electr...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep02193
更新日期:2013-01-01 00:00:00
abstract::The aim of this study was to fabricate a novel polymer-free everolimus-eluting stent with nanostructure using a femtosecond laser (FSL). The stent were coated with everolimus (EVL) using FSL and electrospinning processes. The surface was rendered hydrophobic, which negatively affected both platelet adhesion (82.1%) an...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-25629-9
更新日期:2018-05-09 00:00:00
abstract::A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-019-46785-6
更新日期:2019-07-17 00:00:00
abstract::Epilepsy is a chronic neurological disease with a variable therapeutic response. To design effective treatment strategies for epilepsy, it is important to understand treatment responses and predictive factors. However, limited data are available in Africa, including Ethiopia. The aim of this study was therefore to ass...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-52574-y
更新日期:2019-11-07 00:00:00
abstract::Leber congenital amaurosis (LCA) is a genetically and clinically heterogeneous disease, and represents the most severe form of inherited retinal dystrophy (IRD). The present study reports the mutation spectra and frequency of known LCA and IRD-associated genes in 34 Japanese families with LCA (including three families...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-26524-z
更新日期:2018-05-29 00:00:00
abstract::The high theoretical capacity and low discharge potential of silicon have attracted much attention on Si-based anodes. Herein, hollow porous SiO2 nanocubes have been prepared via a two-step hard-template process and evaluated as electrode materials for lithium-ion batteries. The hollow porous SiO2 nanocubes exhibited ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep01568
更新日期:2013-01-01 00:00:00
abstract::The blood-based diagnosis has a potential to provide an alternative approach for easy diagnosis of Alzheimer's disease (AD) with less invasiveness and low-cost. However, present blood-based AD diagnosis mainly focuses on measuring the plasma Aβ level because no other biomarkers are found to possess evident transport m...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep15703
更新日期:2015-10-27 00:00:00
abstract::Quantifying multi-molecular complex assembly in specific cytoplasmic compartments is crucial to understand how cells use assembly/disassembly of these complexes to control function. Currently, biophysical methods like Fluorescence Resonance Energy Transfer and Fluorescence Correlation Spectroscopy provide quantitative...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep28822
更新日期:2016-06-30 00:00:00