A5022991955- Cancer, Hypoxia, and Metabolism
- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- Ubiquitin and proteasome pathways
- Genetics, Bioinformatics, and Biomedical Research
- Adrenal and Paraganglionic Tumors
- Estrogen and related hormone effects
- Cancer Genomics and Diagnostics
- Biomedical Text Mining and Ontologies
- Inflammatory mediators and NSAID effects
- Breast Cancer Treatment Studies
- Glioma Diagnosis and Treatment
- Hormonal Regulation and Hypertension
- Cancer Cells and Metastasis
- Click Chemistry and Applications
- Gene expression and cancer classification
- Cancer Research and Treatments
- Mitochondrial Function and Pathology
- Cancer therapeutics and mechanisms
- Molecular Biology Techniques and Applications
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Cell Image Analysis Techniques
- Advanced Breast Cancer Therapies
- Cancer, Stress, Anesthesia, and Immune Response
National Institutes of Health
2007-2025
National Cancer Institute
2016-2024
Center for Cancer Research
2018-2024
Frederick National Laboratory for Cancer Research
2022-2023
General Dynamics (United States)
2018-2021
Leidos (United States)
2016-2020
Leidos Biomedical Research Inc. (United States)
2020
ORCID
2018-2019
Government of the United States of America
2018
Office of Science
2017
Batch effects are the systematic non-biological differences between batches (groups) of samples in microarray experiments due to various causes such as sample preparation and hybridization protocols. Previous work focused mainly on development methods for effective batch removal. However, their impact cross-batch prediction performance, which is one most important goals microarray-based applications, has not been addressed. This paper uses a broad selection data sets from Microarray Quality...
Abstract CellMiner Cross-Database (CellMinerCDB, discover.nci.nih.gov/cellminercdb) allows integration and analysis of molecular pharmacological data within across cancer cell line datasets from the National Cancer Institute (NCI), Broad Institute, Sanger/MGH MD Anderson Center (MDACC). We present CellMinerCDB 1.2 with updates to NCI-60, Cell Line Encyclopedia Sanger/MGH, addition new datasets, including NCI-ALMANAC drug combination, MDACC Project proteomic, NCI-SCLC DNA copy number...
CellMinerCDB provides a web-based resource (https://discover.nci.nih.gov/cellminercdb/) for integrating multiple forms of pharmacological and genomic analyses, unifying the richest cancer cell line datasets (the NCI-60, NCI-SCLC, Sanger/MGH GDSC, Broad CCLE/CTRP). enables data queries genomics gene regulatory network exploration pharmacogenomic determinants drug signatures. It leverages overlaps lines drugs across databases to examine reproducibility expand pathway analyses. We illustrate...
Basal p53 levels are tightly suppressed under normal conditions. Disrupting this regulation results in elevated to induce cell cycle arrest, apoptosis, and tumor suppression. Here, we report the suppression of basal by a nuclear, p53-regulated long noncoding RNA that termed PURPL (p53 upregulated regulator levels). Targeted depletion colorectal cancer cells induces growth defects culture mouse xenografts. associates with MYBBP1A, protein binds stabilizes p53, inhibits formation p53-MYBBP1A...
CellMiner-SCLC (https://discover.nci.nih.gov/SclcCellMinerCDB/) integrates drug sensitivity and genomic data, including high-resolution methylome transcriptome from 118 patient-derived small cell lung cancer (SCLC) lines, providing a resource for research into this "recalcitrant cancer." We demonstrate the reproducibility stability of data multiple sources validate SCLC consensus nomenclature on basis expression master transcription factors NEUROD1, ASCL1, POU2F3, YAP1. Our analyses reveal...
Abstract Although several ATR inhibitors are in development, there unresolved questions regarding their differential potency, molecular signatures of patients with cancer for predicting activity, and most effective therapeutic combinations. Here, we elucidate how to improve ATR-based chemotherapy the newly developed inhibitor, M4344 using vitro vivo models. The potency was compared clinically BAY1895344, berzosertib, ceralasertib. anticancer activity investigated as monotherapy combination...
CellMiner (http://discover.nci.nih.gov/cellminer) and CellMinerCDB (https://discover.nci.nih.gov/cellminercdb/) are web-based applications for mining publicly available genomic, molecular, pharmacologic datasets of human cancer cell lines including the NCI-60, Cancer Cell Line Encyclopedia, Genomics Drug Sensitivity in Cancer, Therapeutics Response Portal, NCI/DTP small lung cancer, NCI Almanac line sets. Here, we introduce our RNA sequencing (RNA-seq) data NCI-60 their access integration...
Basal-like breast cancers have several well-characterized distinguishing molecular features, but most of these are features the cancer cells themselves. The unique stromal-epithelial interactions, and more generally, microenvironmental basal-like not been well characterized. To identify characteristic microenvironment cancer, we performed cocultures cell lines with fibroblasts compared luminal fibroblasts. Interactions between induced expression numerous interleukins chemokines, including...
Abstract Background Genomic tests are available to predict breast cancer recurrence and guide clinical decision making. These predictors provide risk scores along with a measure of uncertainty, usually confidence interval. The interval conveys random error not systematic bias. Standard tumor sampling methods make this problematic, as it is common have substantial proportion (typically 30-50%) sample comprised histologically benign tissue. This "normal" tissue could represent source...
Abstract Understanding the mechanisms supporting tumor-initiating cells (TIC) is vital to combat advanced-stage recurrent cancers. Here, we show that in advanced ovarian cancers NFκB signaling via RelB transcription factor supports TIC populations by directly regulating cancer stem-like associated enzyme aldehyde dehydrogenase (ALDH). Loss of significantly inhibited spheroid formation, ALDH expression and activity, chemoresistance, tumorigenesis subcutaneous intrabursal mouse xenograft...
Here we describe a proteomic data resource for the NCI-60 cell lines generated by pressure cycling technology and SWATH mass spectrometry. We developed DIA-expert software to curate visualize data, leading reproducible detection of over 3,100 SwissProt proteotypic proteins systematic quantification pathway activities. Stoichiometric relationships interacting DNA replication, repair, chromatin remodeling NuRD complex, β-catenin, RNA metabolism, prefoldins are more evident than that at mRNA...
The majority of hepatocellular carcinoma develops in the background chronic liver inflammation caused by viral hepatitis and alcoholic or nonalcoholic steatohepatitis. However, impact different types inflammatory microenvironments on phenotypes tumors generated distinct oncogenes is largely unresolved. To address this issue, we murine constitutively active AKT‐1 (AKT) β‐catenin (CAT), followed induction 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC) carbon tetrachloride. Also, DDC‐induced...
Major advances have been made in the field of precision medicine for treating cancer. However, many open questions remain that need to be answered realize goal matching every patient with cancer most efficacious therapy. To facilitate these efforts, we developed CellMinerCDB: National Center Advancing Translational Sciences (NCATS; https://discover.nci.nih.gov/rsconnect/cellminercdb_ncats/), which makes available activity information 2,675 drugs and compounds, including multiple nononcology...
Abstract Current treatment options for metastatic adrenocortical carcinoma (ACC) have limited efficacy, despite the common use of mitotane and cytotoxic agents. This study aimed to identify novel therapeutic ACC. An extensive drug screen was conducted compounds with potential activity against ACC cell lines. We further investigated mechanism action identified compound, TAK-243, its synergistic effects current therapeutics, efficacy in models including patient-derived organoids mouse...
Abstract The recalcitrant nature of triple-negative breast cancer (TNBC) calls for novel treatments. Acetalax (oxyphenisatin acetate) and bisacodyl, which have been are extensively used orally as laxatives, recently reported to exhibit selective antiproliferative activity when incubated with cells xenograft models. Here we show that they both preferentially active in TNBC cell lines, their patterns overlap across the 1000 lines Sanger database but unique distinct from standard...
<p>Implication of the mitochondrial pathways in cellular responses to Acetalax assessed by CRISPR (Achilles project, DepMap MIT) survival comparisons with activity [GDSC_MGH-Sanger, −log<sub>10</sub>(IC<sub>50</sub>M)]. <b>A,</b> Schematic GSEA analysis workflow used generate <b>B</b>. <b>B,</b> determine enriched categories 18,121 genes from comparison [−log<sub>10</sub>(IC<sub>50</sub>M)] for TNBC...
<p>Scatter plots of gene transcript levels versus acetalax activity for genes from the Figure 6 multivariate analysis.</p>
<p>GSEA of RNA-seq for PDX HBCx-185 treated with Acetalax or bisacodyl. <b>A,</b> treatment at 4 hours (left plot) and 24 (right as compared no drug controls. <b>B,</b> Bisacodyl For all experiments, four to five mice were used biological replicates both the All categories shown have significant enrichment (<i>P</i> < 0.0008).</p>
<p><i>In vivo</i> response to Acetalax and bisacodyl in PDX models of TNBC. <b>A, </b><i>In antitumor effect administered at 100, 200, 300 mg/kg the HBCx-158 model. Mean ± standard deviation (<i>n</i> = 4–6 mice/group). ****, <i>P</i> < 0.0001 (Kruskal–Wallis test). <b>B,</b> Waterfall plot showing percentage tumor volume changes xenografts treated with (200 mg/kg) 18 different models. Each bar represents a single...
<p>Scatter plots of ErSO drug activity versus acetalax and TRPM4 gene transcript levels.</p>