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106 results for “BRAF inhibitors”
Study of Selective BRAF Kinase Inhibitor Dabrafenib Monotherapy Twice Daily and in Combination With Dabrafenib Twice Daily and Trametinib Once Daily in Combination Therapy in Subjects With BRAF V600E
ClinicalTrials.gov study NCT01336634. IPD Sharing: YES. Countries: 11. Publications: 5.
MITF/miR-579-3p novel regulatory axis controls BRAF-mutated melanoma decision between cell senescence or progression upon exposure to MAPK inhibitors.
<p><strong>Abstract</strong></p> <p>Therapy of metastatic melanoma has improved dramatically over the last years thanks to the development of targeted therapies (MAPK inhibitors) and immunotherapies. However, drug resistance continues to be a major limitation to the efficacy of these therapies. Our research group has provided robust evidence as to the involvement of a set of microRNAs in the development of resistance to target therapy in BRAF-mutated melanoma cell lines. Among them, a pivotal role is played by miR-579-3p, whose role as oncosuppressor was discovered by our group some years ago. Here we show that miR-579-3p and the microphthalmia-associated transcription factor (MITF) influence reciprocally their expression through positive feedback regulatory loops. In particular we show that miR-579-3p is specifically deregulated in BRAF-mutant melanomas and that its expression levels mirror those of MITF. Luciferase and ChIP studies show that MITF is a positive regulator of miR-579-3p, which is located in the intron 11 of the human gene ZFR (Zink-finger recombinase) and is co-transcribed with its host gene. Moreover, miR-579-3p, by targeting BRAF is able to stabilize MITF protein thus inducing its own transcription. As a consequence, upon exposure to MAPK inhibitors or, alternatively upon miR-579-3p transfection, the activation of this newly uncovered miR-579-3p/MITF axis induces a potent block of proliferation and senescence of BRAF-mutant melanoma cells. Moreover, the long term development of resistance to MAPKi is able to select cells characterized by the loss of both miR-579-3p and MITF and the same down-regulation is also present in patients relapsing after targeted therapies treatments. Altogether these findings suggest that miR-579-3p/MITF interplay potentially governs the balance between proliferation, senescence and resistance to target therapies in BRAF-mutant melanomas.</p> <p><strong>KEYWORDS: </strong></p> <p><strong>Acknowledgements</strong></p> <p>This study was supported by Italian Association for Cancer Research (AIRC) grants IG19865 to G. Ciliberto and IG24451 to R. Mancini and by the Lazio Innova grants 2018 n. 85-2017-13750 and 2020 n. A0375-2020-36657 to R. Mancini and by Italian Minister of Health grant PRIN 2017 (Prot. 2017HWTP2K) to G. Ciliberto and R. Mancini, by Italian Minister of Health through “Ricerca Corrente” grant L2/1 to P.A. Ascierto. The study was also supported by Lega Italiana per la Lotta ai Tumori (LILT) grant n. 2021U0001637 to L. Fattore. We thank all patients who donated samples for this research.</p>
BRAF Inhibitor, Vemurafenib, in Patients With Relapsed or Refractory Hairy Cell Leukemia
ClinicalTrials.gov study NCT01711632. IPD Sharing: Not stated. Countries: 1. Publications: 2.
An Open-Label Phase II Study of the Combination of GSK2118436 and GSK1120212 in Patients With Metastatic Melanoma Which is Refractory or Resistant to BRAF Inhibitor
ClinicalTrials.gov study NCT01619774. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Study to Determine the Effectiveness of GSK1120212 in BRAF Mutation-positive Melanoma Previously Treated With or Without a BRAF Inhibitor
ClinicalTrials.gov study NCT01037127. IPD Sharing: Not stated. Countries: 2. Publications: 1.
Fig. 4 in Characterization of undescribed melanoma inhibitors from Euphorbia mauritanica L. cultivated in Egypt targeting BRAF and MEK 1 kinases via in-silico study and ADME prediction
Fig. 4. Experimental and TDDFT-simulated electronic circular dichroism spctra of (A) euphomauritanol A (1), (B) euphomauritanol B (2), and euphomauritanophane A (3).
Fig. 6 in Characterization of undescribed melanoma inhibitors from Euphorbia mauritanica L. cultivated in Egypt targeting BRAF and MEK 1 kinases via in-silico study and ADME prediction
Fig. 6. Bioavailability radar chart from Swiss ADME online web tool for compounds (A) 1, (B) 2 and (C) 3. The pink area represents the range of the optimal property values for oral bioavailability and the red line is compounds (A) 1, (B) 2 and (C) 3 predicted properties. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
Fig. 5 in Characterization of undescribed melanoma inhibitors from Euphorbia mauritanica L. cultivated in Egypt targeting BRAF and MEK 1 kinases via in-silico study and ADME prediction
Fig. 5. (A) 2D binding mode, (B) 3D binding mode of Euphomauritanol A (1) in the active site of BRaf Kinase V600E (PDB ID: 4XV2) (C) 2D binding mode, and (D) 3D binding mode of euphomauritanophane A (3) in the active site of MEK 1 kinase (PDB ID: 4LMN).
Clinical Trial of Phenformin in Combination With BRAF Inhibitor + MEK Inhibitor for Patients With BRAF-mutated Melanoma
ClinicalTrials.gov study NCT03026517. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Neoadjuvant Use of Talimogene Laherparepvec and BRAF/MEK Inhibitor for Advanced Nodal BRAF Mutant Melanoma
ClinicalTrials.gov study NCT03972046. IPD Sharing: NO. Countries: 1. Publications: 10.
Circulating Melanoma Cells in Metastatic Patients Treated With Selective BRAF Inhibitors
ClinicalTrials.gov study NCT01878396. IPD Sharing: Not stated. Countries: 1. Publications: 5.
Enhancing Radioiodine (RAI) Incorporation Into BRAF Mutant, RAI-Refractory Thyroid Cancers With the BRAF Inhibitor Vemurafenib: A Pilot Study
ClinicalTrials.gov study NCT02145143. IPD Sharing: Not stated. Countries: 1. Publications: 1.
HDAC Inhibitor Vorinostat in Resistant BRAF V600 Mutated Advanced Melanoma
ClinicalTrials.gov study NCT02836548. IPD Sharing: UNDECIDED. Countries: 1. Publications: 1.
Dabrafenib and Trametinib for BRAF-inhibitor Pretreated Patients
ClinicalTrials.gov study NCT02296996. IPD Sharing: Not stated. Countries: 1. Publications: 1.
A Phase II Study of the BRAF Inhibitor, Vemurafenib, Plus Obinutuzumab in Patients With Previously Untreated Classical Hairy Cell Leukemia
ClinicalTrials.gov study NCT03410875. IPD Sharing: UNDECIDED. Countries: 1. Publications: 1.
Long-term Outcome After Vemurafenib / BRAF Inhibitors Interruption in Erdheim-chester Disease
ClinicalTrials.gov study NCT02089724. IPD Sharing: Not stated. Countries: 2. Publications: 3.
Fig. 7. Predicted Boiled-Egg plot from Swiss ADME online web tool for compounds 1–3 in Characterization of undescribed melanoma inhibitors from Euphorbia mauritanica L. cultivated in Egypt targeting BRAF and MEK 1 kinases via in-silico study and ADME prediction
Fig. 7. Predicted Boiled-Egg plot from Swiss ADME online web tool for compounds 1–3.
Fig. 1 in Characterization of undescribed melanoma inhibitors from Euphorbia mauritanica L. cultivated in Egypt targeting BRAF and MEK 1 kinases via in-silico study and ADME prediction
Fig. 1. Chemical structures of isolated compounds (1–11).
Fig. 3 in Characterization of undescribed melanoma inhibitors from Euphorbia mauritanica L. cultivated in Egypt targeting BRAF and MEK 1 kinases via in-silico study and ADME prediction
Fig. 3. Significant NOESY correlations of diterpenoids 1–3.
Fig. 2. Significant 1H 1H in Characterization of undescribed melanoma inhibitors from Euphorbia mauritanica L. cultivated in Egypt targeting BRAF and MEK 1 kinases via in-silico study and ADME prediction
Fig. 2. Significant 1H 1H COSY and HMBC correlations of diterpenoids 1–3.
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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.