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5,016
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5,016 results for “THERAPEUTICS”
Targeting AEBP1 to mitigate pro-tumor activity of cancer-associated fibroblasts and increase therapeutic efficacy to anti-PD-1
GEO Series GSE301078. Mus musculus. 12 samples. Type: Expression profiling by high throughput sequencing.
Therapeutically Applicable Research to Generate Effective Treatments (TARGET)
The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program applies a comprehensive genomic approach to determine molecular changes that drive childhood cancers. The goal of the program is to use data to guide the development of effective, less toxic therapies. TARGET is organized into a collaborative network of disease-specific project teams.
Full transcriptome analysis reveals key regulatory networks and potential therapeutic targets of dorsal root ganglion in rats with painful diabetic peripheral neuropathy
GEO Series GSE305770. Rattus norvegicus. 10 samples. Type: Expression profiling by high throughput sequencing.
Pre-clinical evaluation of cysteamine bitartrate as a therapeutic agent for mitochondrial respiratory chain disease (human)
GEO Series GSE119699. Homo sapiens. 20 samples. Type: Expression profiling by high throughput sequencing.
Characterization of the interaction between SARS-CoV-2 Membrane Protein and Proliferating Cell Nuclear Antigen (PCNA) as a Potential Therapeutic Target
<p>In this dataset, we have validated and explored the interaction between the SARS-CoV-2 M protein and the cellular protein PCNA, an interaction that was previously described by another proteomics study (Gordon et al., 2020). PCNA is an important nuclear protein involved in DNA replication and repair in the cell. The M-protein-PCNA interaction characterized here impacted the cell physiology, including increased localization of PCNA in the cytoplasm and associated DNA damage markers. These phenomena may have consequences for the fate of cells infected with SARS-CoV-2 and for the outcomes of COVID-19, such as persistent DNA damage after the infection. Finally, we show that inhibitors of PCNA and cell nuclear transport present effects in SARS-CoV-2 replication in vitro. Similar results have been presented by other RNA viruses in the literature. In sum, this study sheds light on novel molecular mechanisms of SARS-CoV-2 replication.</p>
Link to dataset related to article "Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target "
<p>This record contains raw data related to article “Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target"</p> <p>Abstract:</p> <p><strong>Background & aims: </strong> The landscape and function of the immune infiltrate of intrahepatic cholangiocarcinoma (iCCA), a rare, yet aggressive tumor of the biliary tract, remains poorly characterized, limiting development of successful immunotherapies. Herein, we aimed to define the molecular characteristics of tumor-infiltrating leukocytes with a special focus on CD4+ regulatory T cells (Tregs).</p> <p><strong>Methods: </strong> We used high-dimensional single-cell technologies to characterize the T-cell and myeloid compartments of iCCA tissues, comparing these with their tumor-free peritumoral and circulating counterparts. We further used genomics and cellular assays to define the iCCA-specific role of a novel transcription factor, mesenchyme homeobox 1 (MEOX1), in Treg biology.</p> <p><strong>Results: </strong> We found poor infiltration of putative tumor-specific CD39+ CD8+ T cells accompanied by abundant infiltration of hyperactivated CD4+ Tregs. Single-cell RNA-sequencing identified an altered network of transcription factors in iCCA-infiltrating compared to peritumoral T cells, suggesting reduced effector functions by tumor-infiltrating CD8+ T cells and enhanced immunosuppression by CD4+ Tregs. Specifically, we found that expression of MEOX1 was highly enriched in tumor-infiltrating Tregs, and demonstrated that MEOX1 overexpression is sufficient to reprogram circulating Tregs to acquire the transcriptional and epigenetic landscape of tumor-infiltrating Tregs. Accordingly, enrichment of the MEOX1-dependent gene program in Tregs was strongly associated with poor prognosis in a large cohort of patients with iCCA.</p> <p><strong>Conclusions: </strong> We observed abundant infiltration of hyperactivated CD4+ Tregs in iCCA tumors along with reduced CD8+ T-cell effector functions. Interfering with hyperactivated Tregs should be explored as an approach to enhance antitumor immunity in iCCA.</p> <p><strong>Lay summary: </strong> Immune cells have the potential to slow or halt the progression of tumors. However, some tumors, such as intrahepatic cholangiocarcinoma, are associated with very limited immune responses (and infiltration of cancer-targeting immune cells). Herein, we show that a specific population of regulatory T cells (a type of immune cell that actually suppresses the immune response) are hyperactivated in intrahepatic cholangiocarcinoma. Targeting these cells could enable cancer-targeting immune cells to act more effectively and should be looked at as a potential therapeutic approach to this aggressive cancer type.</p>
Rescue of lysosomal function as therapeutic strategy for SPG15 hereditary spastic paraplegia
<p>Raw data from the research article "Rescue of lysosomal function as therapeutic strategy for SPG15 hereditary spastic paraplegia".</p>
Dataset related to article "Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target"
<p>This record contains raw data related to article “Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target"</p> <p>Abstract</p> <p><strong>Background & aims: </strong> The landscape and function of the immune infiltrate of intrahepatic cholangiocarcinoma (iCCA), a rare, yet aggressive tumor of the biliary tract, remains poorly characterized, limiting development of successful immunotherapies. Herein, we aimed to define the molecular characteristics of tumor-infiltrating leukocytes with a special focus on CD4+ regulatory T cells (Tregs).</p> <p><strong>Methods: </strong> We used high-dimensional single-cell technologies to characterize the T-cell and myeloid compartments of iCCA tissues, comparing these with their tumor-free peritumoral and circulating counterparts. We further used genomics and cellular assays to define the iCCA-specific role of a novel transcription factor, mesenchyme homeobox 1 (MEOX1), in Treg biology.</p> <p><strong>Results: </strong> We found poor infiltration of putative tumor-specific CD39+ CD8+ T cells accompanied by abundant infiltration of hyperactivated CD4+ Tregs. Single-cell RNA-sequencing identified an altered network of transcription factors in iCCA-infiltrating compared to peritumoral T cells, suggesting reduced effector functions by tumor-infiltrating CD8+ T cells and enhanced immunosuppression by CD4+ Tregs. Specifically, we found that expression of MEOX1 was highly enriched in tumor-infiltrating Tregs, and demonstrated that MEOX1 overexpression is sufficient to reprogram circulating Tregs to acquire the transcriptional and epigenetic landscape of tumor-infiltrating Tregs. Accordingly, enrichment of the MEOX1-dependent gene program in Tregs was strongly associated with poor prognosis in a large cohort of patients with iCCA.</p> <p><strong>Conclusions: </strong> We observed abundant infiltration of hyperactivated CD4+ Tregs in iCCA tumors along with reduced CD8+ T-cell effector functions. Interfering with hyperactivated Tregs should be explored as an approach to enhance antitumor immunity in iCCA.</p> <p><strong>Lay summary: </strong> Immune cells have the potential to slow or halt the progression of tumors. However, some tumors, such as intrahepatic cholangiocarcinoma, are associated with very limited immune responses (and infiltration of cancer-targeting immune cells). Herein, we show that a specific population of regulatory T cells (a type of immune cell that actually suppresses the immune response) are hyperactivated in intrahepatic cholangiocarcinoma. Targeting these cells could enable cancer-targeting immune cells to act more effectively and should be looked at as a potential therapeutic approach to this aggressive cancer type.</p> <p> </p>
Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target
<p>Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target</p> <p> </p> <p>Abstract</p> <p><strong>Background & aims: </strong>The landscape and function of the immune infiltrate of intrahepatic cholangiocarcinoma (iCCA), a rare, yet aggressive tumor of the biliary tract, remains poorly characterized, limiting development of successful immunotherapies. Herein, we aimed to define the molecular characteristics of tumor-infiltrating leukocytes with a special focus on CD4+ regulatory T cells (Tregs).</p> <p><strong>Methods: </strong>We used high-dimensional single-cell technologies to characterize the T-cell and myeloid compartments of iCCA tissues, comparing these with their tumor-free peritumoral and circulating counterparts. We further used genomics and cellular assays to define the iCCA-specific role of a novel transcription factor, mesenchyme homeobox 1 (MEOX1), in Treg biology.</p> <p><strong>Results: </strong>We found poor infiltration of putative tumor-specific CD39+ CD8+ T cells accompanied by abundant infiltration of hyperactivated CD4+ Tregs. Single-cell RNA-sequencing identified an altered network of transcription factors in iCCA-infiltrating compared to peritumoral T cells, suggesting reduced effector functions by tumor-infiltrating CD8+ T cells and enhanced immunosuppression by CD4+ Tregs. Specifically, we found that expression of MEOX1 was highly enriched in tumor-infiltrating Tregs, and demonstrated that MEOX1 overexpression is sufficient to reprogram circulating Tregs to acquire the transcriptional and epigenetic landscape of tumor-infiltrating Tregs. Accordingly, enrichment of the MEOX1-dependent gene program in Tregs was strongly associated with poor prognosis in a large cohort of patients with iCCA.</p> <p><strong>Conclusions: </strong>We observed abundant infiltration of hyperactivated CD4+ Tregs in iCCA tumors along with reduced CD8+ T-cell effector functions. Interfering with hyperactivated Tregs should be explored as an approach to enhance antitumor immunity in iCCA.</p> <p><strong>Lay summary: </strong>Immune cells have the potential to slow or halt the progression of tumors. However, some tumors, such as intrahepatic cholangiocarcinoma, are associated with very limited immune responses (and infiltration of cancer-targeting immune cells). Herein, we show that a specific population of regulatory T cells (a type of immune cell that actually suppresses the immune response) are hyperactivated in intrahepatic cholangiocarcinoma. Targeting these cells could enable cancer-targeting immune cells to act more effectively and should be looked at as a potential therapeutic approach to this aggressive cancer type.</p> <p> </p>
Dataset related to article "Digital single-operator cholangioscopy in diagnostic and therapeutic bilio-pancreatic diseases: A prospective, multicenter study "
<p>This record contains raw data related to article “Digital single-operator cholangioscopy in diagnostic and therapeutic bilio-pancreatic diseases: A prospective, multicenter study"</p> <p><strong>Background and aim: </strong> Digital single-operator cholangioscopy (D-SOC) is an endoscopic procedure that is increasingly used for the management of bilio-pancreatic diseases. We aimed to investigate the efficacy and safety of D-SOC for diagnostic and therapeutic indications.</p> <p><strong>Methods: </strong> This is a multicenter, prospective study(January 2016-June 2019) across eighteen tertiary centers. The primary outcome was procedural success of D-SOC. Secondary outcomes were: D-SOC visual assessment and diagnostic yield of SpyBite biopsy in cases of biliary strictures, stone clearance rate in cases of difficult biliary stones, rate of adverse events(AEs) for all indications.</p> <p><strong>Results: </strong> D-SOC was performed in 369 patients (201(54,5%) diagnostic and 168(45,5%)therapeutic). Overall, procedural success rate was achieved in 360(97,6%) patients. The sensitivity, specificity, PPV, NPV and accuracy in biliary strictures were: 88,5%, 77,3%, 83,3%, 84,1% and 83,6% for D-SOC visual impression; 80,2%, 92,6%, 95,1%, 72,5% and 84,7% for the SpyBite biopsy, respectively. For difficult biliary stones, complete duct clearance was obtained in 92,1% patients (82,1% in a single session). Overall, AEs occurred in 37(10%) cases.The grade of AEs was mild or moderate for all cases, except one which was fatal.</p> <p><strong>Conclusion: </strong> D-SOC is effective for diagnostic and therapeutic indications.Most of the AEs were minor and managed conservatively, even though a fatal event has happened that is not negligible and should be considered before using D-SOC.</p>
Pre-clinical spheroid models identify BMX as a therapeutic target for metastatic MYCN non-amplified neuroblastoma
<p>The development of targeted therapies has provided new hope for an increasing number of cancer patients affected by previously incurable diseases. The clinical success of this approach, however, is limited by numerous challenges, including a better control of cell plasticity, particularly in refractory and metastatic patients. Here we addressed this question in Neuroblastoma (NB), an aggressive pediatric malignancy, which remains a clinical challenge for high-risk patients. NB originates from neural crest-derived progenitors through defective differentiation programs combined with oncogenic activity due to genetic and epigenetic alterations. In order to identify critical genes responsible for tumor aggressiveness we performed combined chromatin and transcriptome analyses on matched primary xenografts, spheroids and differentiated adherent cultures, which we derived from metastatic non-<em>MYCN</em> amplified (nMNA) NB patients. Our approach identified the kinase <em>BMX</em> among the most differentially regulated genes between patient-derived xenografts and spheroids versus adherent models. We further found that <em>BMX</em> expression is associated with high tumor stage and poor patient survival in multiple NB transcriptomic datasets and critical to maintain the self-renewal and tumorigenic potential of NB spheroids. Moreover, we uncovered a positive correlation between <em>BMX </em>expression and the mesenchymal tumor cell phenotype, which was previously associated with increased chemo-resistance. Finally, we show that BMX inhibitors can readily reverse this cellular state, increase the sensitivity of NB spheroids toward standard of care chemotherapy, and reduce tumor growth in preclinical NB models. Altogether, our study identifies BMX as a novel promising therapeutic target for high-risk patients with relapsed or refractory nMNA NB tumors.</p>
Dataset related to article "Implementing Pre-Therapeutic UGT1A1 Genotyping in Clinical Practice: A Real-Life Study"
<p>This record contains raw data related to article “Implementing Pre-Therapeutic<em> UGT1A1</em> Genotyping in Clinical Practice: A Real-Life Study"</p> <p>Current guidelines recommend pre-therapeutic <em>UGT1A1</em> genotyping to guide irinotecan dosing, but the usefulness of this approach remains to be clarified. In 247 patients with advanced gastrointestinal cancers undergoing irinotecan-based chemotherapy, we prospectively performed <em>UGT1A1*28</em> genotyping and we analyzed the incidence of severe neutropenia according to genotype-guided dose reductions. Overall, 28 (11.3%) and 92 (37.2%) patients were homozygous or heterozygous <em>UGT1A1*28</em> carriers, respectively. Grade ≥ 3 neutropenia was reported in 39% of homozygous patients receiving an upfront dose reduction of irinotecan (median 40%, range 22-58%), in 20% of heterozygous or wild-type patients receiving full dose (OR<sub>vs*28/*28 genotype</sub> = 0.38; 95% CI: 0.14-1.03; <em>p</em> = 0.058), and in 15.3% of those receiving a reduced dose for clinical reasons (OR <sub>vs*28/*28 genotype</sub> = 0.28, 95% IC: 0.12-0.67; <em>p</em> = 0.004). Occurrence of severe neutropenia was inversely associated with dose reduction in <em>UGT1A1*28</em> homozygous carriers (OR<sub>x10 unit</sub> = 0.62, 95% CI: 0.27-1.40, <em>p</em> = 0.249) and <em>UGT1A1</em> heterozygous or wild-type patients (OR<sub>x10 unit</sub> = 0.87, 95% CI: 0.59-1.28, <em>p</em> = 0.478). Incidence of severe neutropenia was related to irinotecan doses and <em>UGT1A1</em> polymorphisms. Upfront irinotecan dose reductions do not reduce the burden of grade ≥ 3 neutropenia in <em>UGT1A1*28</em> homozygous carriers.</p>
Pre-therapeutic Analysis of the Individual Radiosensitivity of Cancer Patients in Luxembourg (APRI-Lux): Prospective National Interventional Study With Minimal Risk
ClinicalTrials.gov study NCT05433974. IPD Sharing: UNDECIDED. Countries: 0. Publications: 0.
Therapeutic immune cell engineering with an mRNA : AAV-Sleeping Beauty composite system
GEO Series GSE206291. Homo sapiens. 4 samples. Type: Other.
High-throughput quantification of cell-surface proteins for accelerated cancer therapeutic discovery
GEO Series GSE268052. Homo sapiens. 21 samples. Type: Other.
The Role of CDCP1 in Carotid Artery Stenosis: Implications for Mitochondrial Autophagy and Therapeutic Potential of 8-isopentenylnaringenin
GEO Series GSE285538. Rattus. 6 samples. Type: Expression profiling by high throughput sequencing.
Comprehensive transcriptome profiling of ulcerative colitis mouse model suggests biomarkers and therapeutic targets for human colitis [RNA-Seq]
GEO Series GSE155301. Mus musculus. 12 samples. Type: Expression profiling by high throughput sequencing.
Identifying therapeutic vulnerability in ataxia telangiectasia and Rad3-related protein (ATR) inhibitor resistant splicing factor mutant myeloid malignancies
GEO Series GSE213935. Homo sapiens. 20 samples. Type: Expression profiling by high throughput sequencing.
Pharmacologic inhibition of BAF chromatin remodeling complexes as a therapeutic approach to transcription factor-dependent cancers
GEO Series GSE241450. Homo sapiens. 119 samples. Type: Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Other.
S100A9 Overexpression Drives Chemoresistance and Poor Prognosis in AML with Adavivint as a Targeted Therapeutic
GEO Series GSE283851. Homo sapiens. 18 samples. Type: Expression profiling by high throughput sequencing.
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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.