A high-content image analysis approach for quantitative measurements of chemosensitivity in patient-derived tumor microtissues.

Abstract:

:Organotypic, three-dimensional (3D) cancer models have enabled investigations of complex microtissues in increasingly realistic conditions. However, a drawback of these advanced models remains the poor biological relevance of cancer cell lines, while higher clinical significance would be obtainable with patient-derived cell cultures. Here, we describe the generation and data analysis of 3D microtissue models from patient-derived xenografts (PDX) of non-small cell lung carcinoma (NSCLC). Standard of care anti-cancer drugs were applied and the altered multicellular morphologies were captured by confocal microscopy, followed by automated image analyses to quantitatively measure phenotypic features for high-content chemosensitivity tests. The obtained image data were thresholded using a local entropy filter after which the image foreground was split into local regions, for a supervised classification into tumor or fibroblast cell types. Robust statistical methods were applied to evaluate treatment effects on growth and morphology. Both novel and existing computational approaches were compared at each step, while prioritizing high experimental throughput. Docetaxel was found to be the most effective drug that blocked both tumor growth and invasion. These effects were also validated in PDX tumors in vivo. Our research opens new avenues for high-content drug screening based on patient-derived cell cultures, and for personalized chemosensitivity testing.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Ahonen I,Åkerfelt M,Toriseva M,Oswald E,Schüler J,Nees M

doi

10.1038/s41598-017-06544-x

subject

Has Abstract

pub_date

2017-07-26 00:00:00

pages

6600

issue

1

issn

2045-2322

pii

10.1038/s41598-017-06544-x

journal_volume

7

pub_type

杂志文章
  • Massive gene loss in mistletoe (Viscum, Viscaceae) mitochondria.

    abstract::Parasitism is a successful survival strategy across all kingdoms and has evolved repeatedly in angiosperms. Parasitic plants obtain nutrients from other plants and some are agricultural pests. Obligate parasites, which cannot complete their lifecycle without a host, may lack functional photosystems (holoparasites), or...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep17588

    authors: Petersen G,Cuenca A,Møller IM,Seberg O

    更新日期:2015-12-02 00:00:00

  • Systematic Analysis of Pigeons' Discrimination of Pixelated Stimuli: A Hierarchical Pattern Recognition System Is Not Identifiable.

    abstract::Pigeons learned to discriminate two different patterns displayed with miniature light-emitting diode arrays. They were then tested with 84 interspersed, non-reinforced degraded pattern pairs. Choices ranged between 100% and 50% for one or other of the patterns. Stimuli consisting of few pixels yielded low choice score...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-50212-1

    authors: Delius JD,Delius JAM

    更新日期:2019-09-26 00:00:00

  • Lighting up ultraviolet fluorescence from chicken albumen through plasmon resonance energy transfer of gold nanoparticles.

    abstract::Au nanoparticles (AuNPs), which easily aggregate in organic thin film, are observed to well-disperse in chicken albumen thin films. The incorporated AuNPs is distributed uniformly inside the thin film and is as dense as 650 (particles/μm(3)). In addition, enhanced ultraviolet (UV) fluorescence centered at 350 nm is ob...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep01505

    authors: Tsung Chen I,Chang PH,Chang YC,Guo TF

    更新日期:2013-01-01 00:00:00

  • A memristive plasticity model of voltage-based STDP suitable for recurrent bidirectional neural networks in the hippocampus.

    abstract::Memristive systems have gained considerable attention in the field of neuromorphic engineering, because they allow the emulation of synaptic functionality in solid state nano-physical systems. In this study, we show that memristive behavior provides a broad working framework for the phenomenological modelling of cellu...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-27616-6

    authors: Diederich N,Bartsch T,Kohlstedt H,Ziegler M

    更新日期:2018-06-19 00:00:00

  • Erratum: Corrigendum: Investigating starch gelatinization through Stokes vector resolved second harmonic generation microscopy.

    abstract::Scientific Reports 7: Article number: 45816; published online: 06 April 2017; updated: 16 May 2017. The original version of this Article contained an error in Affiliation 2, which was incorrectly given as: 'Department of Biophysics, School of Life Sciences, Manipal University, Manipal, 567014, India'. ...

    journal_title:Scientific reports

    pub_type: 已发布勘误

    doi:10.1038/srep46803

    authors: Mazumder N,Xiang LY,Qiu J,Kao FJ

    更新日期:2017-05-16 00:00:00

  • Surgical Outcomes of Patients with Diagnostic Preoperative Monocular Occlusion in Intermittent Exotropia.

    abstract::We evaluated surgical outcomes of bilateral rectus (BLR) recession in patients with intermittent exotropia who underwent diagnostic monocular occlusion. Records of patients with intermittent exotropia who were preoperatively examined one-hour monocular occlusion and underwent BLR recession were reviewed retrospectivel...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-64642-9

    authors: Lee JY,Song JE,Chang HR,Choi CY,Han SY

    更新日期:2020-05-08 00:00:00

  • Early antibody response and clinical outcome in experimental canine leishmaniasis.

    abstract::Infected dogs are the main reservoir of zoonotic visceral leishmaniasis, a widespread parasitic disease caused by Leishmania infantum. Therefore, the control of canine infections is required to reduce the incidence of human cases. Disease outcome in dogs depends on the fine balance between parasite virulence and effic...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-55087-w

    authors: Olías-Molero AI,Corral MJ,Jiménez-Antón MD,Alunda JM

    更新日期:2019-12-09 00:00:00

  • Relationship between TEC jumps and auroral substorm in the high-latitude ionosphere.

    abstract::The influence of an auroral substorm on the total electron content (TEC) jumps and cycle slips on Global Positioning System (GPS) at high-latitudes is studied. For the first time, optical data from the all-sky imager, as well as interplanetary magnetic field and magnetometer data are used to complete the analysis of t...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-63422-9

    authors: Chernyshov AA,Miloch WJ,Jin Y,Zakharov VI

    更新日期:2020-04-14 00:00:00

  • Lifespan and functionality of mycorrhizal fungal mycelium are uncoupled from host plant lifespan.

    abstract::Arbuscular mycorrhizal fungi (AMF) are obligate symbionts, living in associations with the roots of most land plants. AMF produce wide networks of extraradical mycelium (ERM) of indeterminate length, spreading from host roots into the surrounding soil and establishing belowground interconnections among plants belongin...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-28354-5

    authors: Pepe A,Giovannetti M,Sbrana C

    更新日期:2018-07-06 00:00:00

  • The Regulation of Exosporium-Related Genes in Bacillus thuringiensis.

    abstract::Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis (Bt) are spore-forming members of the Bacillus cereus group. Spores of B. cereus group species are encircled by exosporium, which is composed of an external hair-like nap and a paracrystalline basal layer. Despite the extensive studies on the structure of...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep19005

    authors: Peng Q,Kao G,Qu N,Zhang J,Li J,Song F

    更新日期:2016-01-25 00:00:00

  • Evidence for ice-ocean albedo feedback in the Arctic Ocean shifting to a seasonal ice zone.

    abstract::Ice-albedo feedback due to the albedo contrast between water and ice is a major factor in seasonal sea ice retreat, and has received increasing attention with the Arctic Ocean shifting to a seasonal ice cover. However, quantitative evaluation of such feedbacks is still insufficient. Here we provide quantitative eviden...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-08467-z

    authors: Kashiwase H,Ohshima KI,Nihashi S,Eicken H

    更新日期:2017-08-15 00:00:00

  • Disorder and defects are not intrinsic to boron carbide.

    abstract::A unique combination of useful properties in boron-carbide, such as extreme hardness, excellent fracture toughness, a low density, a high melting point, thermoelectricity, semi-conducting behavior, catalytic activity and a remarkably good chemical stability, makes it an ideal material for a wide range of technological...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep19330

    authors: Mondal S,Bykova E,Dey S,Ali SI,Dubrovinskaia N,Dubrovinsky L,Parakhonskiy G,van Smaalen S

    更新日期:2016-01-18 00:00:00

  • DRP3 and ELM1 are required for mitochondrial fission in the liverwort Marchantia polymorpha.

    abstract::Mitochondria increase in number by the fission of existing mitochondria. Mitochondrial fission is needed to provide mitochondria to daughter cells during cell division. In Arabidopsis thaliana, four kinds of genes have been reported to be involved in mitochondrial fission. Two of them, DRP3 (dynamin-related protein3) ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-04886-0

    authors: Nagaoka N,Yamashita A,Kurisu R,Watari Y,Ishizuna F,Tsutsumi N,Ishizaki K,Kohchi T,Arimura SI

    更新日期:2017-07-04 00:00:00

  • Chemical and structural stability of lithium-ion battery electrode materials under electron beam.

    abstract::The investigation of chemical and structural dynamics in battery materials is essential to elucidation of structure-property relationships for rational design of advanced battery materials. Spatially resolved techniques, such as scanning/transmission electron microscopy (S/TEM), are widely applied to address this chal...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep05694

    authors: Lin F,Markus IM,Doeff MM,Xin HL

    更新日期:2014-07-16 00:00:00

  • Impact of diverse chemotherapeutic agents and external factors on activation of brown adipose tissue in a large patient collective.

    abstract::Increased activity of brown adipose tissue (BAT) activity in adults is thought to prevent obesity. Therefore, regulators of BAT activity might serve as anti-obesity therapy in future, but are not investigated thoroughly up to now. In our study, we assessed retrospectively the association of BAT activity with several e...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-37924-6

    authors: Brendle C,Stefan N,Stef I,Ripkens S,Soekler M,la Fougère C,Nikolaou K,Pfannenberg C

    更新日期:2019-02-13 00:00:00

  • Metabolomic and lipidomic profile in men with obstructive sleep apnoea: implications for diagnosis and biomarkers of cardiovascular risk.

    abstract::The use of metabolomic and lipidomic strategies for selecting potential biomarkers for obstructive sleep apnoea (OSA) has been little explored. We examined adult male patients with OSA (defined by an apnoea-hypopnoea index ≥15 events/hour), as well as age-, gender-, and fat-composition-matched volunteers without OSA. ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-29727-6

    authors: Lebkuchen A,Carvalho VM,Venturini G,Salgueiro JS,Freitas LS,Dellavance A,Martins FC,Lorenzi-Filho G,Cardozo KHM,Drager LF

    更新日期:2018-07-26 00:00:00

  • New insights into the cellular responses to iron nanoparticles in Capsicum annuum.

    abstract::In this study, the anatomical and ultrastructural responses of Capsicum annuum to iron nanoparticles (Fe NPs) were determined. The results showed that the bio-effects of Fe NPs on plants could be positive or negative, depending on the additive concentrations. Low concentrations of Fe NPs were found to promote plant gr...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-18055-w

    authors: Yuan J,Chen Y,Li H,Lu J,Zhao H,Liu M,Nechitaylo GS,Glushchenko NN

    更新日期:2018-02-19 00:00:00

  • Improving the performance of bright quantum dot single photon sources using temporal filtering via amplitude modulation.

    abstract::Single epitaxially-grown semiconductor quantum dots have great potential as single photon sources for photonic quantum technologies, though in practice devices often exhibit nonideal behavior. Here, we demonstrate that amplitude modulation can improve the performance of quantum-dot-based sources. Starting with a brigh...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep01397

    authors: Ates S,Agha I,Gulinatti A,Rech I,Badolato A,Srinivasan K

    更新日期:2013-01-01 00:00:00

  • Sodium-activated potassium channels shape peripheral auditory function and activity of the primary auditory neurons in mice.

    abstract::Potassium (K+) channels shape the response properties of neurons. Although enormous progress has been made to characterize K+ channels in the primary auditory neurons, the molecular identities of many of these channels and their contributions to hearing in vivo remain unknown. Using a combination of RNA sequencing and...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-39119-z

    authors: Reijntjes DOJ,Lee JH,Park S,Schubert NMA,van Tuinen M,Vijayakumar S,Jones TA,Jones SM,Gratton MA,Xia XM,Yamoah EN,Pyott SJ

    更新日期:2019-02-22 00:00:00

  • Gene mutation associated with esl mediates shifts on fungal community composition in rhizosphere soil of rice at grain-filling stage.

    abstract::Generally, plant roots shape the rhizosphere fungal community but how individual plant genes involved in senescence affect this shaping is less studied. We used an early senescence leaf (esl) mutant rice and compared it with its isogenic wild type variety to evaluate the effect of the vacuolar H+-ATPase (VHA-A1) gene ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-35578-y

    authors: Letuma P,Arafat Y,Waqas M,Lin F,Lin W,Zhang Y,Masita M,Fan K,Li Z,Lin W

    更新日期:2018-11-30 00:00:00

  • Camouflaged Nanosilver with Excitation Wavelength Dependent High Quantum Yield for Targeted Theranostic.

    abstract::The present study shows the thorough investigations on optical properties and hydrodynamic diameters of glutathione (GSH) stabilized nanosilver clusters (AgNC) at different stages of synthesis and engineering for the optimized absolute quantum yield to generate fluorescent images of Dalton Lymphoma Ascites (DLA) tumou...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-34843-4

    authors: Girigoswami A,Yassine W,Sharmiladevi P,Haribabu V,Girigoswami K

    更新日期:2018-11-07 00:00:00

  • A novel bispecific antibody platform to direct complement activity for efficient lysis of target cells.

    abstract::Harnessing complement-mediated cytotoxicity by therapeutic antibodies has been limited because of dependency on size and density of antigen, structural constraints resulting from orientation of antibody binding, and blockade of complement activation by inhibitors expressed on target cells. We developed a modular bispe...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-48461-1

    authors: Cruz JW,Damko E,Modi B,Tu N,Meagher K,Voronina V,Gartner H,Ehrlich G,Rafique A,Babb R,Aneja P,Potocky TB,D' Orvilliers A,Coppi A,E SY,Qiu H,Williams CM,Bennett BL,Chen G,Macdonald L,Olson W,Lin JC,Stahl N,Mu

    更新日期:2019-08-19 00:00:00

  • Genome dynamics and evolution of Salmonella Typhi strains from the typhoid-endemic zones.

    abstract::Typhoid fever poses significant burden on healthcare systems in Southeast Asia and other endemic countries. Several epidemiological and genomic studies have attributed pseudogenisation to be the major driving force for the evolution of Salmonella Typhi although its real potential remains elusive. In the present study,...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep07457

    authors: Baddam R,Kumar N,Shaik S,Lankapalli AK,Ahmed N

    更新日期:2014-12-12 00:00:00

  • The eastern extent of seasonal iron limitation in the high latitude North Atlantic Ocean.

    abstract::The availability of iron (Fe) can seasonally limit phytoplankton growth in the High Latitude North Atlantic (HLNA), greatly reducing the efficiency of the biological carbon pump. However, the spatial extent of seasonal iron limitation is not yet known. We present autumn nutrient and dissolved Fe measurements, combined...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-37436-3

    authors: Birchill AJ,Hartner NT,Kunde K,Siemering B,Daniels C,González-Santana D,Milne A,Ussher SJ,Worsfold PJ,Leopold K,Painter SC,Lohan MC

    更新日期:2019-02-05 00:00:00

  • Impact of nutritional supplements on cognitive development of children in developing countries: A meta-analysis.

    abstract::Nutritional supplements may be important on cognition but the evidence is heterogeneous. This meta-analysis aimed (1) to determine whether nutritional supplements provided to pregnant women or young children could improve cognitive development of children in developing countries, and (2) to explore how supplementation...

    journal_title:Scientific reports

    pub_type: 杂志文章,meta分析

    doi:10.1038/s41598-017-11023-4

    authors: Ip P,Ho FKW,Rao N,Sun J,Young ME,Chow CB,Tso W,Hon KL

    更新日期:2017-09-06 00:00:00

  • Hair follicle germs containing vascular endothelial cells for hair regenerative medicine.

    abstract::Hair regenerative medicine has emerged as a promising approach for the treatment of severe hair loss. Recent advances in three-dimensional tissue engineering, such as formation of hair follicle germs (HFGs), have considerably improved hair regeneration after transplantation in animal models. Here, we proposed an appro...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-79722-z

    authors: Kageyama T,Chun YS,Fukuda J

    更新日期:2021-01-12 00:00:00

  • Axonal blockage with microscopic magnetic stimulation.

    abstract::Numerous neurological dysfunctions are characterized by undesirable nerve activity. By providing reversible nerve blockage, electric stimulation with an implanted electrode holds promise in the treatment of these conditions. However, there are several limitations to its application, including poor bio-compatibility an...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-74891-3

    authors: Skach J,Conway C,Barrett L,Ye H

    更新日期:2020-10-22 00:00:00

  • Modified serpinA1 as risk marker for Parkinson's disease dementia: Analysis of baseline data.

    abstract::Early detection of dementia in Parkinson disease is a prerequisite for preventive therapeutic approaches. Modified serpinA1 in cerebrospinal fluid (CSF) was suggested as an early biomarker for differentiation between Parkinson patients with (PDD) or without dementia (PD). Within this study we aimed to further explore ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep26145

    authors: Halbgebauer S,Nagl M,Klafki H,Haußmann U,Steinacker P,Oeckl P,Kassubek J,Pinkhardt E,Ludolph AC,Soininen H,Herukka SK,Wiltfang J,Otto M

    更新日期:2016-05-17 00:00:00

  • MicroPattern: a web-based tool for microbe set enrichment analysis and disease similarity calculation based on a list of microbes.

    abstract::The microbiota colonized on human body is renowned as "a forgotten organ" due to its big impacts on human health and disease. Recently, microbiome studies have identified a large number of microbes differentially regulated in a variety of conditions, such as disease and diet. However, methods for discovering biologica...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep40200

    authors: Ma W,Huang C,Zhou Y,Li J,Cui Q

    更新日期:2017-01-10 00:00:00

  • Bacteria forming drag-increasing streamers on a drop implicates complementary fates of rising deep-sea oil droplets.

    abstract::Competing time scales involved in rapid rising micro-droplets in comparison to substantially slower biodegradation processes at oil-water interfaces highlights a perplexing question: how do biotic processes occur and alter the fates of oil micro-droplets (<500 μm) in the 400 m thick Deepwater Horizon deep-sea plume? F...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-61214-9

    authors: White AR,Jalali M,Boufadel MC,Sheng J

    更新日期:2020-03-09 00:00:00