Abstract:
:Neuroblastoma is the most commonly diagnosed extracranial tumor in the first year of life. Approximately 9% of neuroblastoma patients present germline or somatic aberrations in the gene encoding for anaplastic lymphoma kinase (ALK). This increases in high-risk neuroblastomas, which have a 14% frequency of ALK aberrations at the time of diagnosis and show increasing numbers at relapse. Abrogating ALK activity with kinase inhibitors is employed as clinical therapy in malignancies such as non-small cell lung cancer and has shown good results in pediatric inflammatory myofibroblastic tumors and anaplastic large cell lymphomas. A phase I clinical trial of the first generation ALK inhibitor, crizotinib, in neuroblastoma patients showed modest results and suggested that further investigation was needed. Continuous development of ALK inhibitors has resulted in the third generation inhibitor repotrectinib (TPX-0005), which targets the active kinase conformations of ALK, ROS1 and TRK receptors. In the present study we investigated the effects of repotrectinib in a neuroblastoma setting in vitro and in vivo. Neuroblastoma cell lines were treated with repotrectinib to investigate inhibition of ALK and to determine its effect on proliferation. PC12 cells transfected with different ALK mutant variants were used to study the efficacy of repotrectinib to block ALK activation/signaling. The in vivo effect of repotrectinib was also analyzed in a neuroblastoma xenograft model. Our results show that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Cervantes-Madrid D,Szydzik J,Lind DE,Borenäs M,Bemark M,Cui J,Palmer RH,Hallberg Bdoi
10.1038/s41598-019-55060-7subject
Has Abstractpub_date
2019-12-18 00:00:00pages
19353issue
1issn
2045-2322pii
10.1038/s41598-019-55060-7journal_volume
9pub_type
杂志文章abstract::At the Ediacaran/Cambrian boundary, ecosystems witnessed an unparalleled biological innovation: the appearance of shelled animals. Here, we report new paleoecological and paleobiological data on Cloudina, which was one of the most abundant shelled animals at the end of the Ediacaran. We report the close association of...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-05753-8
更新日期:2017-07-14 00:00:00
abstract::Gait is an important health indicator and poor gait is strongly associated with disability and risk of falls. Thyroid dysfunction is suggested as a potential determinant of gait deterioration, but this has not been explored in a population-based study. We therefore investigated the association of thyroid function with...
journal_title:Scientific reports
pub_type: 临床试验,杂志文章
doi:10.1038/srep38912
更新日期:2016-12-14 00:00:00
abstract::The work describes the development of a flexible, hydrogel embedded pH-sensor that can be integrated in inexpensive wearable and non-invasive devices at epidermal level for electrochemical quantification of H+ ions in sweat. Such a device can be useful for swift, real time diagnosis and for monitoring specific conditi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-45399-2
更新日期:2019-06-20 00:00:00
abstract::Targeted protein degradation (TPD) through a proteasome-dependent pathway induced by heterofunctional small molecules is initiated by the formation of a ternary complex with recruited E3 ligases. This complex formation affects the degradation ability of TPD molecules, and thus we tested for visualization of the intrac...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-59966-5
更新日期:2020-02-20 00:00:00
abstract::Neutrophil extracellular traps (NETs) extruded from neutrophils upon activation are composed of chromatin associated with cytosolic and granular proteins, which ensnare and kill microorganisms. This microbicidal mechanism named classical netosis has been shown to dependent on reactive oxygen species (ROS) generation b...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep18302
更新日期:2015-12-17 00:00:00
abstract::Doubly curved nanofiber-reinforced optically transparent composites with low thermal expansion of 15 ppm/k are prepared by hot pressing vacuum-filtered Pickering emulsions of hydrophobic acrylic resin monomer, hydrophilic chitin nanofibers and water. The coalescence of acrylic monomer droplets in the emulsion is preve...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep16421
更新日期:2015-11-10 00:00:00
abstract::Optogenetics allows precise, fast and reversible intervention in biological processes. Light-sheet microscopy allows observation of the full course of Drosophila embryonic development from egg to larva. Bringing the two approaches together allows unparalleled precision into the temporal regulation of signaling pathway...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-16879-0
更新日期:2017-11-30 00:00:00
abstract::Previous studies have suggested that microRNA-107 (miR-107) regulates cell migration in tumor and promotes Hypoxia Inducible Factor 1α (HIF1α) regulated angiogenesis under hypoxia. We found that miR-107 was strongly expressed in ischemic boundary zone (IBZ) after permanent middle cerebral artery occlusion (pMCAO) in r...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep13316
更新日期:2015-08-21 00:00:00
abstract::New monosaccharide-based lipid A analogues were rationally designed through MD-2 docking studies. A panel of compounds with two carboxylate groups as phosphates bioisosteres, was synthesized with the same glucosamine-bis-succinyl core linked to different unsaturated and saturated fatty acid chains. The binding of the ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-37421-w
更新日期:2019-01-29 00:00:00
abstract::Glutamate dehydrogenase (GDH) is a key enzyme interlinking carbon and nitrogen metabolism. Recent discoveries of the GDH specific role in breast cancer, hyperinsulinism/hyperammonemia (HI/HA) syndrome, and neurodegenerative diseases have reinvigorated interest on GDH regulation, which remains poorly understood despite...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-73743-4
更新日期:2020-10-05 00:00:00
abstract::Reproductive investment generally involves a trade-off between somatic growth and energy allocation for reproduction. Previous studies have inferred that jumbo squid Dosidicus gigas support growth during maturation through continuous feeding (an "income" source). However, our recent work suggests possible remobilizati...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-66703-5
更新日期:2020-06-15 00:00:00
abstract::The ideal strategy for hair cell regeneration is promoting residual supporting cell proliferation followed by induction of hair cell differentiation. In this study, cultured neonatal mouse organs of Corti were treated with neomycin to eliminate hair cells followed by incubation with recombined adenovirus expressing Pa...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep02996
更新日期:2013-10-21 00:00:00
abstract::Capacitation is the final maturation step spermatozoa undergo prior to fertilisation. The efflux of cholesterol from the sperm membrane to the extracellular environment is a crucial step during capacitation but current methods to quantify this process are suboptimal. In this study, we validate the use of a BODIPY-chol...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-45831-7
更新日期:2019-07-08 00:00:00
abstract::Nonalcoholic steatohepatitis (NASH) is a hepatic phenotype of the metabolic syndrome, and increases the risk of cirrhosis and hepatocellular carcinoma (HCC). Although increasing evidence points to the therapeutic implications of certain types of anti-diabetic agents in NASH, it remains to be elucidated whether their e...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-57935-6
更新日期:2020-01-22 00:00:00
abstract::Long-term daylight deprivation such as during the Antarctic winter has been shown to lead to delayed sleep timing and sleep fragmentation. We aimed at testing whether retinal sensitivity, sleep and circadian rest-activity will change during long-term daylight deprivation on two Antarctic bases (Concordia and Halley VI...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-33450-7
更新日期:2018-11-01 00:00:00
abstract::Ooids are typically spherical sediment grains characterised by concentric layers encapsulating a core. There is no universally accepted explanation for ooid genesis, though factors such as agitation, abiotic and/or microbial mineralisation and size limitation have been variously invoked. Here we examine the possible i...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-18908-4
更新日期:2018-01-11 00:00:00
abstract::We have developed an optimized protocol for plasma targeted mRNA sequencing in our previous study. Here, we performed plasma targeted mRNA sequencing for 40 colorectal adenoma patients and 39 colonoscopy-proven normal controls in order to find potential circulating mRNA markers for colorectal adenoma. Results showed t...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-49445-x
更新日期:2019-09-10 00:00:00
abstract::Empirical yield estimation from satellite data has long lacked suitable combinations of spatial and temporal resolutions. Consequently, the selection of metrics, i.e., temporal descriptors that predict grain yield, has likely been driven by practicality and data availability rather than by systematic targetting of cri...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-51715-7
更新日期:2019-10-31 00:00:00
abstract::Circulating tumor cells (CTC) have been studied extensively in various tumor types and are a well-established prognosticator in colorectal cancer (CRC). This is the first study to isolate CTC directly from the tumor outflow in secondary lung tumors. For this purpose in 24 patients with CRC who underwent pulmonary meta...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-26410-8
更新日期:2018-06-08 00:00:00
abstract::Pandanus odorifer (Forssk) Kuntze grows naturally along the coastal regions and withstands salt-sprays as well as strong winds. A combination of omics approaches and enzyme activity studies was employed to comprehend the mechanistic basis of high salinity tolerance in P. odorifer. The young seedlings of P. odorifer we...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-37039-y
更新日期:2019-01-30 00:00:00
abstract::Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. T...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-29011-7
更新日期:2018-08-01 00:00:00
abstract::Human learners can generalize a new concept from a small number of samples. In contrast, conventional machine learning methods require large amounts of data to address the same types of problems. Humans have cognitive biases that promote fast learning. Here, we developed a method to reduce the gap between human beings...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-25679-z
更新日期:2018-05-09 00:00:00
abstract::Charge separation is a critical process for achieving high efficiencies in organic photovoltaic cells. The initial tightly bound excitonic electron-hole pair has to dissociate fast enough in order to avoid photocurrent generation and thus power conversion efficiency loss via geminate recombination. Such process takes ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-04621-9
更新日期:2017-06-27 00:00:00
abstract::Available epidemiological reports on follicular lymphoma (FL) often highlight a significant discrepancy between its high and low incidence rates in Western and Eastern Europe, respectively. The reasons behind that difference are not fully understood, but underreporting is typically presumed as one of the main factors....
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-71579-6
更新日期:2020-09-03 00:00:00
abstract::Carbon fiber-synthetic foam core sandwich composites are widely used for many structural applications due to their superior mechanical performance and low weight. Unfortunately these structures typically have very poor acoustic performance. There is increasingly growing demand in mitigating this noise issue in sandwic...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep00403
更新日期:2012-01-01 00:00:00
abstract::In this study, we sought to enhance the cutting properties of the various blades by coating them with Zr- and Fe-based thin film metallic glasses (TFMGs) to a thickness of 234-255 nm via sputter deposition. In oil-repellency/sliding tests on kitchen blades, the sliding angle and friction forces were as follows: bare b...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-52054-3
更新日期:2019-10-29 00:00:00
abstract::No consensus currently exist on the optimal treatment of patients with high-risk nonmuscle invasive (HGT1) micropapillary variant of bladder cancer (MPBC). Transcripsome analysis may allow stratification of MPBC-HGT1 enabling prediction of recurrence and guide therapeutic management for individual patients. Whole tran...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-76904-7
更新日期:2020-11-18 00:00:00
abstract::Fatty alcohols have been identified as promising organic phase change materials (PCMs) for thermal energy storage, because of their suitable temperature range, nontoxicity and can be obtained from both natural and synthetic sources. Like all other organic PCMs, octadecanol (OD) as PCM suffers from low thermal conducti...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-64149-3
更新日期:2020-06-08 00:00:00
abstract::Many chemical reactions in biological cells occur at very low concentrations of constituent molecules. Thus, transcriptional gene-regulation is often controlled by poorly expressed transcription-factors, such as E.coli lac repressor with few tens of copies. Here we study the effects of inherent concentration fluctuati...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep17820
更新日期:2015-12-04 00:00:00
abstract::Phaseonium is a three-level Λ quantum system, in which a coherent microwave and an optical control (pump) beams can be used to actively modulate the dielectric response. Here we propose a new metamaterial structure comprising of a periodic array of triangular phaseonium metamolecules arranged as a trefoil. We present ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep21083
更新日期:2016-02-16 00:00:00