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6,222 results for “small cells”
Study of Oral cMET Inhibitor INC280 in Patients With EGFR Wild-type (wt), Advanced Non-small Cell Lung Cancer (NSCLC) (Geometry Mono-1)
ClinicalTrials.gov study NCT02414139. IPD Sharing: YES. Countries: 20. Publications: 3.
Development of a high-throughput small molecule screening assay for phenotypical characterization of lysosomal storage disorder-affected cells, with infantile cystinosis as a proof of principle
<p>Together with the Pivot Park Screening Centre we performed a drug screen on CTNS-/- proximal tubule cells. For this we developed an assay to evaluate LC3-II positive puncta, and which may be applied for any disease in which autophagy plays an important role. The screen was optimized by the hotel for a 384 well format, making it useful for high throughput screening. The screen was performed with 1280 compounds from the Prestwick library.</p>
Improved small-angle x-ray scattering of nanoparticle self-assembly using a cell with a flat liquid surface
<p>One important way of forming nanostructures entails the assembly of nanoparticle (NP) monolayers at a liquid surface. Probing this assembly of 11.8-nm-diameter iron oxide NPs by small-angle x-ray scattering (SAXS) is studied using cells with walls at angles designed to significantly reduce the size of the meniscus. This enables the collection of much larger signals in the SAXS images of ordered arrays of NPs at liquid/gas interfaces, as is needed for kinetics studies and x-ray exposure minimization, along with the observation of extremely high degrees of order. Meniscus flattening and improved signal collection are demonstrated for the assembly of ordered arrays of iron oxide NP monolayers at a diethylene glycol surface.</p>
Supplementary Material: HIV-1-Induced Small T Cell Syncytia Can Transfer Virus Particles to Target Cells through Transient Contacts
<p>Videos supplementary to <em>Viruses</em> <strong>2015</strong>, <em>7</em>(12), 6590-6603; doi:10.3390/v7122959</p> <p><strong>Captions:</strong></p> <p><strong>Movie S1.</strong> <strong>HIV-1-infected cells in the lymph node of humanized mice.</strong></p> <p>Humanized BLT mice were injected in the footpad with HIV-nGFP, where GFP is highly enriched in cellular nuclei, and the draining popliteal lymph node prepared for MP-IVM at day 2. Representative infected cells (GFP+; green) that display one, two or three discernible nuclei are shown (<strong>top</strong>). In the bottom panels, green fluorescence signals above 80% of the intensity maximum were used to define cell nuclei, which are shown in white. The syncytium with two discernible nuclei remains elongated throughout the recording, while the syncytium with three discernible nuclei switches between coordinated and uncoordinated motility. Each individual frame is a maximum intensity projection of 11 <em>z</em>-stacks spaced 4 μm apart (for a total volume of 40 μm). Time is shown in minutes and seconds. Scale bar = 20 μm. See also Figure 1A.</p> <p><strong>Movie S2.</strong> <strong>Syncytia in the lymph node contact uninfected T cells without undergoing cell-cell fusion</strong>.</p> <p><em>In vitro</em>-generated central memory CD4+ T cells, either infected with HIV-GFP (GFP+; green) or uninfected (labeled with CellTracker Orange; red), were adoptively transferred by footpad injection into BLT mice pretreated with antiretroviral drugs (100 mg/kg FTC, 150 mg/kg TDF). After 12 h, the draining popliteal lymph node was prepared for MP-IVM. Two representative movies of T cell migration prior to (yellow circle) and during<br /> (blue circle) transient interactions with syncytia are shown, demonstrating cellular interactions without fusion. Each individual frame is a maximum intensity projection of 11 <em>z</em>-stacks spaced 4 μm apart (for a total volume of 40 μm). Time is shown in minutes and seconds. Scale bar = 40 μm. See also Figure 1F,G.</p> <p><strong>Movie S3.</strong> <strong>CD4</strong><strong>+ T cells in 3D culture form small syncytia with elongated morphology</strong>.</p> <p>Primary human CD4+ T cells isolated from a healthy donor were infected with VSV-G-pseudotyped NL4-3<sup>Gag-iGFP</sup> virus. The next day, cells were embedded in a 3D collagen gel as described in the Experimental Section, and 12 h later imaged live at 37 °C using a 20× objective on a DeltaVision widefield microscope. Six 3 µm-spaced Z-slices were taken every 20 s, and were subsequently projected into one image. The syncytium seen here in green has two nuclei located at opposite ends, and a central bulged region with high amounts of viral Gag. The diffuse fluorescence is a result of this syncytium being located at a higher part of the gel, where the limitations of widefield imaging become more prominent. See also Figure 2A.</p> <p><strong>Movie S4.</strong> <strong>Small CEM-SS syncytia in 3D culture can dynamically change their morphology</strong>.</p> <p>CEM-SS cells were infected with VSV-G-pseudotyped NL4-3<sup>Gag-iGFP</sup> virus. The next day, cells were embedded in a 3D Matrigel gel as described in the Experimental Section, and 24 h later imaged live at 37 °C using a<br /> 40× objective on a DeltaVision widefield microscope. Seven 2 μm-spaced Z-slices were taken every 5 min, and were subsequently projected into one image. A syncytium with two nuclei (dark areas within the cell in the GFP channel) begins with two lobes, which merge into a coordinated round morphology as the cell begins to migrate through the gel and leaves the plane of focus. See also Figure 2B.</p> <p><strong>Movie S5.</strong> <strong>CD4</strong><strong>+ T cells in 3D culture exhibit </strong><strong><em>in vivo</em>-like migratory behavior</strong>.</p> <p>Primary human CD4<sup>+</sup> T cells were infected, embedded in collagen, and imaged as in Movie S3 (though with a<br /> 10 s time lapse). The uninucleated infected cell migrating across the field moves by 108 μm over 560 s, for a mean velocity of 11.58 μm/min. Such fast directed amoeboid motility is not typically observed in classical 2D culture and requires the presence of a 3D ECM. See also Figure 2C.</p> <p><strong>Movie S6.</strong> <strong>Uninucleated infected cells and syncytia can transfer virus to target cells without fusion.</strong></p> <p>CEM-SS cells were infected, embedded in Matrigel, and imaged as in Movie S4. Virus transfer from a uninucleated infected cell (top) and a syncytium (bottom left) to a number of target cells (denoted by T) can be seen here.<br /> The uninucleated infected cell transfers virus to target cells T1–T5, and the syncytium transfers virus to target cells T6–T7. Images shown represent brightfield in gray (bottom right), or Gag-iGFP in green, shown either with normal scaling (bottom left, and merged with brightfield at top right), or with a 0.6 gamma correction applied and enhanced scaling to better show appearance of Gag-iGFP puncta on target cells (top left). Scale bar = 30 μm. A yellow arrow indicates the moment where the uninucleated infected cell begins transferring virus to target cells T1–T3, and all of the other transfer events in this field are happening at roughly the same time. At this time, Gag-iGFP puncta appear to distribute between cells T1–T3 in a progressive fashion, beginning from the point of contact with the infected cell (see also Figure 3A, middle panel). Cells T4 and T5 also receive virus particles from this infected cell, and T4 can be seen migrating away at the end. Also note a trail of released virus left behind by the uninucleated infected cell as it migrates from left to right from 08:00:00 to 09:10:00 (see also Movies S7 and S9, Figure 4 for similar events in syncytia). The syncytium’s targets, T6 and T7, are already in intimate contact with it at the start of the movie, and are obscured by lobes of the syncytium. At the 10:45:00 mark, cell T6 breaks free from the syncytium, now harboring a large amount of virus particles on its surface, as the syncytium slowly migrates away, and cell T7 also appears to harbor virus particles on its surface by the final time point.</p> <p><strong>Movie S7.</strong> <strong>A virus transfer event between a syncytium and two uninfected target cells.</strong></p> <p>CEM-SS cells were infected, embedded in Matrigel, and imaged as in Movies S4 and S6. The syncytium shown here initially has two nuclei, but soon fuses with an uninfected cell and now has three clearly visible nuclei. It remains stationary for several hours, before beginning to migrate towards a pair of uninfected target cells (top). Very soon after contact, virus particles can be seen covering the surface of both cells, one of which eventually migrates away. See also Figure 3A (left panel). Note also another instance of a dense accumulation of cell-free virus particles in what appears to be a pocket within the hydrogel that the syncytium moves one of its lobes out of, revealing the deposited free virus, before it moves back into the pocket. See also Figure 4A.</p> <p><strong>Movie S8.</strong> <strong>Cell-to-cell transfer of virus can take place while cells are migrating.</strong></p> <p>CEM-SS cells were infected, later mixed with CMAC-labeled uninfected CEM-SS cells (shown in blue), embedded in collagen, and imaged as above. A syncytium with two nuclei (one of which bears CMAC signal, indicating that it formed recently and not before the infected culture was mixed with the labeled uninfected cells) migrates across the field. Its trailing edge contacts an uninfected CMAC-labeled cell, which is then dragged along with it, and finally dropped in the corner of the field. The target cell now bears virus particles on its surface, and is no longer in contact with the syncytium, which has moved into a different focal plane and stopped migrating (not shown). The image was refocused at the 10:30:00 mark to better show the target cell and the virus particles on its surface. Note that this movie also shows an instance of newly synthesized Gag-iGFP appearing in a previously uninfected cell (not the target cell contacted by the syncytium). This non-CMAC labeled uninfected cell appears in the bottom left of the field at 07:20:00 and exhibits steadily increasing diffuse intracellular signal, as documented in Figure 3A (right) and Figure 3B,C (green traces).</p> <p><strong>Movie S9.</strong> <strong>Migrating infected cells can deposit a trail of released virus particles</strong>.</p> <p>CEM-SS cells were infected, embedded in Matrigel, and imaged as in Movies S4, S6, and S7. A syncytium with 3 nuclei switches into a coordinated morphology and begins migrating across the field. Released virus particles can be seen in its wake (also shown enlarged and with increased brightness as an inset). Shortly after the end of the movie, the cell-free virus accumulation appeared to dissipate (not shown), but it could not be determined whether this was because of photobleaching or if they had in fact diffused away. See also Figure 4B.</p>
Identification of a small molecule Tim-3 inhibitor to potentiate T cell-mediated antitumor immunotherapy in preclinical models
<p><span>T cell immunoglobulin and mucin-containing molecule 3 (Tim-3), expressed in dysfunctional and exhausted T cells, has been widely acknowledged as a promising immune checkpoint target for tumor immunotherapy. Here, using a strategy combining virtual and functional screening, we identified a compound named ML-T7 that targets the FG-CC' cleft of Tim-3, a highly conserved binding site of </span><span>phosphatidylserine</span><span> (PtdSer) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). ML-T7 enhanced the survival and antitumor activity of </span><span>primary CD8<sup>+</sup> cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells and reduced their exhaustion </span><span>in vitro and in vivo</span><span>. In addition, ML-T7 promoted NK cells' killing activity and DC antigen-presenting capacity, consistent with the reported activity of Tim-3.</span><span> Notably, ML-T7 strengthened DCs' functions through both Tim-3 and Tim-4, consistent with the hypothesis that Tim-4 contains a similar FG-CC' loop. Intraperitoneal dosing of ML-T7 showed comparable tumor inhibitory effects to Tim-3 blocking antibody. ML-T7 reduced syngeneic tumor progression in both wildtype and Tim-3 humanized mice and alleviated the immunosuppressive microenvironment. Furthermore, combined ML-T7 and anti-PD-1 therapy had greater therapeutic efficacy than monotherapy in mice, supporting further development of ML-T7 for tumor immunotherapy. Our study demonstrates a potential small molecule for selectively blocking Tim-3 and warrants further study.</span></p>
Molecular dynamics dataset for pharmacological repositioning in the treatment of non-small-cell lung cancer
<p><span>Non-small cell lung cancer (NSCLC) is a type of lung cancer associated with translocation of the EML4 and ALK genes on the short arm of chromosome 2. This leads to the development of an aberrant protein kinase with a deregulated catalytic domain, the cdALK<sup>+</sup>. Currently, different ALK inhibitors (iALKs) have been proposed to treat ALK<sup>+ </sup>NSCLC patients.</span> <span>However, the recent resistance to iALKs stimulates the exploration of new iALKs for NSCLC. Here, we describe an <em>in silico</em> approach to finding FDA-approved drugs that can be used by pharmacological repositioning as iALK. We used homology modelling to obtain a structural model of cdALK<sup>+</sup> protein and then performed molecular docking and molecular dynamics of the complex cdALK<sup>+</sup>-iALKs to generate the pharmacophore model. The pharmacophore was used to identify potential iALKs from FDA-approved drugs library by ligand-based virtual screening. Four pharmacophores with different atomistic characteristics were generated, resulting in six drugs that satisfied the proposed atomistic positions</span> <span>and coupled at the ATP-binding site. Mitoxantrone, riboflavin and abacavir exhibit the best interaction energies with 228.29, 165.40 and 133.48 kjoul/mol respectively. In addition, the special literature proposed these drugs for other types of diseases due to pharmacological repositioning. This study proposes FDA-approved drugs with ALK inhibitory characteristics. Moreover, we identified pharmacophores sites that can be tested with other pharmacological libraries</span><span>.</span></p>
Data supporting 'Small molecule and cell contact-inducible systems for controlling expression and differentiation in stem cells'
<p>Data supporting Soliman et al. 2024. Manuscript describes data collection practices and experimental design.</p>
Enhancing comparative T-cell receptor repertoire analysis in small biological samples through pooling homologous cell samples from multiple mice
<p>All data files used to generate the figures in the paper are shared in this project.</p> <p>Scripts are available on <a href="https://github.com/i3-unit/CRM_24" target="_blank" rel="noopener">GitHub</a>.</p>
Small scale test-expression of full-length huntingtin Q23 with HAP40 in baculoviral expression system production in sf9 insect cells – 2018/05/14
<p><strong>Project</strong> - Huntingtin structure-function open lab notebook. </p> <p><strong>Experiment and rationale</strong> - Small scale test-expression of full-length huntingtin Q23 with HAP40 in baculoviral expression system production in sf9 insect cells – 2018/05/14. To validate our insect cell production system for the generation of physiologically relevant huntingtin constructs, HTT and HAP40 will be co-expressed and purified from sf9 culture. </p>
Assessment of changes in circRNA expression based on transcripts of genes encoding ADAMTS proteins in patients with non-small cell lung carcinoma compared to normal tissue
Open the record for dataset details and reuse information.
Machine readable code lists for an algorithm to identify incident non-small cell lung cancer (NSCLC) in United States healthcare claims data
<p>Machine readable code lists for an algorithm to identify incident non-small cell lung cancer (NSCLC) in United States healthcare claims data</p>
HINC dataset from: Homeopathic treatment as an add-on therapy may improve quality of life and prolong survival in patients with non-small cell lung cancer: A prospective, randomized, placebo-controlled, double-blind, three-arm, multicenter study
<p class="CxSpFirst"><b>Background:</b> Patients with advanced non-small cell lung cancer (NSCLC) have limited treatment options. Alongside conventional anticancer treatment, additive homeopathy might help to alleviate side effects of conventional therapy. The aim of the present study was to investigate whether additive homeopathy might influence quality of life (QoL) and survival in NSCLC patients.</p> <p class="CxSpMiddle"><b>Methods:</b> In this prospective, randomized, placebo-controlled, double-blind, three-arm, multicenter, phase III study, we evaluated the possible effects of additive homeopathic treatment compared with placebo in NSCLC stage IV patients with respect to QoL in the two randomized groups and survival time in all three groups. Treated patients visited the outpatients' centers every 9 weeks. 150 Patients with stage IV NSCLC were included in the study. 98 received either individualized homeopathic remedies (n=51) or placebo (n=47) in a double-blinded fashion. 52 control patients without any homeopathic treatment were observed for survival only. The constituents of the different homeopathic remedies were mainly of plant, mineral or animal origin. The remedies were manufactured by stepwise dilution and succussion, thereby preparing stable Good Manufacturing Practice grade formulations.</p> <p class="CxSpMiddle"><b>Results:</b> QoL as well as functional and symptom scales showed significant improvement in the homeopathy group when compared with placebo after 9 and 18 weeks of homeopathic treatment (p<0.001). Median survival time was significantly longer in the homeopathy group (435 days) vs placebo (257 days; p=0.010) as well as vs control (228 days; p<0.001). Survival rate in the homeopathy group differed significantly from placebo (p=0.020) and from control (p<0.001).</p> <p class="CxSpMiddle"><b>Conclusion:</b> QoL improved significantly in the homeopathy group compared with placebo. In addition, survival was significantly longer in the homeopathy group versus placebo and control. A higher QoL might have contributed to the prolonged survival. The study suggests that homeopathy positively influences not only QoL but also survival. Further studies including other tumor entities are warranted.</p>
Non-cell autonomous small RNA silencing in Arabidopsis female gametes
<p>Raw data tables as well as R script</p>
Enhanced Mapping of Small Molecule Binding Sites in Cells
<p>Selected docking poses for Wozniak et al manuscript. File name include the structure id (PDBID or Alphafold model) and the probe id, separated by an underscore (i.e., 6tjk_4.pdb, or AF-P10620-F1-model_6.pdb).</p>
Rovalpituzumab Tesirine (SC16LD6.5) in Recurrent Small Cell Lung Cancer
ClinicalTrials.gov study NCT01901653. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Sorafenib in Treating Patients With Extensive Stage Small Cell Lung Cancer
ClinicalTrials.gov study NCT00182689. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Cisplatin/Carboplatin and Etoposide With or Without Nivolumab in Treating Patients With Extensive Stage Small Cell Lung Cancer
ClinicalTrials.gov study NCT03382561. IPD Sharing: Not stated. Countries: 1. Publications: 1.
A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
ClinicalTrials.gov study NCT04256421. IPD Sharing: YES. Countries: 23. Publications: 1.
Non-interventional Study to Assess the Frequency of Cachexia in Patients With Non-small Cell Lung Cancer.
ClinicalTrials.gov study NCT02968979. IPD Sharing: NO. Countries: 1. Publications: 1.
Pembrolizumab Plus Epacadostat vs Pembrolizumab Plus Placebo in Metastatic Non-Small Cell Lung Cancer (KEYNOTE-654-05/ECHO-305-05)
ClinicalTrials.gov study NCT03322540. IPD Sharing: NO. Countries: 18. Publications: 1.
ScienceDex guides
Understand access before you commit
These curated guides explain access requirements, typical timelines, costs, and reuse considerations for widely used research datasets.
Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.