Abstract：
:Developing therapeutics that target multiple receptor signaling pathways in tumors is critical as therapies targeting single specific biomarker/pathway have shown limited efficacy in patients with cancer. In this study, we extensively characterized a bi-functional molecule comprising of epidermal growth factor receptor (EGFR) targeted nanobody (ENb) and death receptor (DR) targeted ligand TRAIL (ENb-TRAIL). We show that ENb-TRAIL has therapeutic efficacy in tumor cells from different cancer types which do not respond to either EGFR antagonist or DR agonist monotherapies. Utilizing pharmacological inhibition, genetic loss of function and FRET studies, we show that ENb-TRAIL blocks EGFR signalling via the binding of ENb to EGFR which in turn induces DR5 clustering at the plasma membrane and thereby primes tumor cells to caspase-mediated apoptosis. In vivo, using a clinically relevant orthotopic resection model of primary glioblastoma and engineered stem cells (SC) expressing ENb-TRAIL, we show that the treatment with synthetic extracellular matrix (sECM) encapsulated SC-ENb-TRAIL alleviates tumor burden and significantly increases survival. This study is the first to report novel mechanistic insights into simultaneous targeting of receptor-mediated proliferation and cell death signaling pathways in different tumor types and presents a promising approach for translation into the clinical setting.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Zhu Y,Bassoff N,Reinshagen C,Bhere D,Nowicki MO,Lawler SE,Roux J,Shah Kdoi
10.1038/s41598-017-02483-9subject
Has Abstractpub_date
2017-06-01 00:00:00pages
2602issue
1issn
2045-2322pii
10.1038/s41598-017-02483-9journal_volume
7pub_type
杂志文章abstract：:We show that filamentous fungi can emit green or red light after the accumulation of particulate lanthanide metal-organic frameworks over the cell wall. These new biohybrids present photoluminescence properties that are unaffected by the components of the cell wall. In addition, the fungal cells internalise lanthanide...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-43835-x
更新日期：2019-05-13 00:00:00
abstract：:The development of electrochemical biosensors for the simultaneous detection of ascorbic acid (AA), dopamine (DA), uric acid (UA), tryptophan (Trp), and nitrite ([Formula: see text]) in human serum is reported in this work. Free-standing graphene nanosheets were fabricated on Ta wire using the chemical vapor depositio...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-07646-2
更新日期：2017-08-01 00:00:00
abstract：:This study focused on the mechanisms that fatty acid conjugating strains - Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 - influence lipid metabolism when ingested with α-linolenic acid (ALA) enriched diet. Four groups of BALB/c mice received ALA enriched diet (3% (w/w)) either alone or in comb...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep43300
更新日期：2017-03-07 00:00:00
abstract：:Hot-iron disbudding, a routine procedure that prevents horn bud growth through cauterization, is painful for calves. The resulting burns remain sensitive to touch for weeks, but it is unknown whether calves experience ongoing, non-evoked pain. We evaluated conditioned place preference for analgesia in 44 calves disbud...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-60260-7
更新日期：2020-03-02 00:00:00
abstract：:Junction-less nanowire transistors are being investigated to solve short channel effects in future CMOS technology. Here we demonstrate 8 nm diameter silicon nanowire junction-less transistors with metallic doping densities which demonstrate clear 1D electronic transport characteristics. The 1D regime allows excellent...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-03138-5
更新日期：2017-06-07 00:00:00
abstract：:Establishing robust genome engineering methods in the malarial parasite, Plasmodium falciparum, has the potential to substantially improve the efficiency with which we gain understanding of this pathogen's biology to propel treatment and elimination efforts. Methods for manipulating gene expression and engineering the...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-77644-4
更新日期：2021-01-11 00:00:00
abstract：:3D printing has produced many beneficial applications for surgery. The technique´s applicability in replicating nasal cavity anatomy for clinical use has not been studied. Our aim was to determine whether 3D printing could realistically replicate the nasal cavities and the airflow passing through them from a clinical ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-57537-2
更新日期：2020-01-16 00:00:00
abstract：:Sesamin is a furofuran-type lignan that is found abundantly in seeds of Sesamum indicum (sesame) and has been widely accepted as a dietary supplement with positive effects on human health. The biological activity of sesamin in human cells and organs has been analysed extensively, although comparatively few studies sho...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-45003-7
更新日期：2019-06-14 00:00:00
abstract：:The relationship between cumulative exposure to resting heart rate (cumRHR) and mortality remain unclear in the general population. In the Kailuan cohort study, resting heart rate (RHR) was repeatedly measured at baseline and at years 2 and 4 by electrocardiogram among 47,311 adults aged 48.70 ± 11.68. The cumRHR was ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep40212
更新日期：2017-01-09 00:00:00
abstract：:Anatase TiO2 has been suggested as a potential sodium anode material, but the low electrical conductivity of TiO2 often limits the rate capability, resulting in poor electrochemical properties. To address this limitation, we propose graphene-wrapped anatase TiO2 nanofibers (rGO@TiO2 NFs) through an effective wrapping ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep13862
更新日期：2015-09-10 00:00:00
abstract：:High Resolution Melt (HRM) is a versatile and rapid post-PCR DNA analysis technique primarily used to differentiate sequence variants among only a few short amplicons. We recently developed a one-vs-one support vector machine algorithm (OVO SVM) that enables the use of HRM for identifying numerous short amplicon seque...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep19218
更新日期：2016-01-18 00:00:00
abstract：:Intractable diseases such as cancer are associated with breakdown in multiple individual functions, which conspire to create unhealthy phenotype-combinations. An important challenge is to decipher how these functions are coordinated in health and disease. We approach this by drawing on dynamical systems theory. We pos...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep21957
更新日期：2016-03-16 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-74629-1
更新日期：2020-10-15 00:00:00
abstract：:Beside its unique nutritional content breast milk also contains live cells from the mother. Fate of these cells in the offspring has not been adequately described. In this study, we aimed to detect and identify maternal cells in the suckling's blood and the brain. Green fluorescent protein expressing transgenic female...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-32715-5
更新日期：2018-09-24 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep15686
更新日期：2015-10-28 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-50586-2
更新日期：2019-09-30 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep06903
更新日期：2014-11-11 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-20945-6
更新日期：2018-02-07 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-12342-2
更新日期：2017-09-20 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep38462
更新日期：2016-12-07 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep21728
更新日期：2016-02-24 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-47844-8
更新日期：2019-08-06 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-23054-6
更新日期：2018-03-16 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2016-04-13 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-10398-8
更新日期：2017-08-30 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep29020
更新日期：2016-07-01 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-06045-x
更新日期：2017-07-18 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-35060-9
更新日期：2018-11-14 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep22460
更新日期：2016-03-03 00:00:00
