A5023493854- Cancer Genomics and Diagnostics
- Radiomics and Machine Learning in Medical Imaging
- Advanced MRI Techniques and Applications
- Medical Imaging Techniques and Applications
- Prostate Cancer Treatment and Research
- Head and Neck Cancer Studies
- Bladder and Urothelial Cancer Treatments
- Renal cell carcinoma treatment
- Prostate Cancer Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Genetic factors in colorectal cancer
- Sarcoma Diagnosis and Treatment
- Neurofibromatosis and Schwannoma Cases
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- Urinary and Genital Oncology Studies
- Soft tissue tumors and treatment
- Molecular Biology Techniques and Applications
- Liver physiology and pathology
- Nuclear Structure and Function
- Genetic and Kidney Cyst Diseases
- Lung Cancer Treatments and Mutations
- CAR-T cell therapy research
- Fibroblast Growth Factor Research
- Extracellular vesicles in disease
Washington University in St. Louis
2014-2025
RELX Group (United States)
2018-2021
Alvin J. Siteman Cancer Center
2014-2016
Harvard University
1986
Boston Children's Hospital
1986
Brandeis University
1981
Universidad Peruana Cayetano Heredia
1981
Abstract Circulating tumor DNA (ctDNA) sensitivity remains subpar for molecular residual disease (MRD) detection in bladder cancer patients. To remedy this problem, we focused on the biofluid most proximal to disease, urine, and analyzed urine 74 localized We integrated ultra-low-pass whole genome sequencing (ULP-WGS) with personalized profiling by deep (uCAPP-Seq) achieve sensitive MRD predict overall survival. Variant allele frequency, inferred mutational burden, copy number-derived...
Background The standard of care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which typically preceded by neoadjuvant chemotherapy. However, the inability to assess minimal residual disease (MRD) noninvasively limits our ability offer bladder-sparing treatment. Here, we sought develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis. Methods and findings We applied Cancer Personalized Profiling Deep Sequencing (uCAPP-Seq), targeted next-generation...
Background The leading cause of mortality for patients with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is development malignant peripheral nerve sheath tumor (MPNST), an aggressive soft tissue sarcoma. In setting NF1, this frequently arises from within its common and benign precursor, plexiform neurofibroma (PN). Transformation PN to MPNST challenging diagnose due difficulties in distinguishing cross-sectional imaging results intralesional heterogeneity resulting...
Abstract Numerous cell states are known to comprise the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME). However, developmental stemness and co-occurrence of these remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on a cohort treatment-naive PDAC time-of-diagnosis endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) samples ( n = 25). We then combined with surgical resection 6) publicly available increase statistical power 80)....
We hypothesized that circulating tumor DNA (ctDNA) molecular residual disease (MRD) analysis without prior mutational knowledge could be performed after neoadjuvant chemotherapy to assess oligometastatic colorectal cancer (CRC) treated surgically with curative intent. also investigated urine as an alternative analyte for ctDNA MRD detection in this nongenitourinary setting.
Hepatocyte growth factor activators (HGFA), matriptase, and hepsin are S1 family trypsin-like serine proteases. These proteases proteolytically cleave the single-chain zymogen precursors, pro-HGF (hepatocyte factor), pro-MSP (macrophage stimulating protein) into active heterodimeric forms. HGF MSP activating ligands for oncogenic receptor tyrosine kinases (RTKs), c-MET RON, respectively. We have discovered first substrate-based ketothiazole inhibitors of HGFA, matriptase hepsin. The...
Abstract Upregulation of the HGF and MSP growth‐factor processing serine endopeptidases HGFA, matriptase hepsin is correlated with increased metastasis in multiple tumor types driven by c‐MET or RON kinase signaling. We rationally designed P1’ α‐ketobenzothiazole mechanism‐based inhibitors these proteases. Structure–activity studies are presented, which resulted identification potent differential selectivity. The tetrapeptide span P1–P1’ substrate cleavage site via a amide linker off...
Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor signaling inhibitors (ARSI) is often lethal. Liquid biopsy biomarkers for this deadly form of disease remain under investigation, and underpinning mechanisms ill-understood.
<div>AbstractPurpose:<p>Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor signaling inhibitors (ARSI) is often lethal. Liquid biopsy biomarkers for this deadly form of disease remain under investigation, and underpinning mechanisms ill-understood.</p>Experimental Design:<p>We applied targeted cell-free DNA (cfDNA) sequencing 126 patients with mCRPC from three academic centers separately performed genome-wide cfDNA methylation on 43...
Polymer-assisted solution-phase (PASP) parallel library synthesis was used to discover a piperazinyl glutamate pyridine as P2Y12 antagonist. Exploitation of this lead provided compounds with excellent inhibition platelet aggregation measured in human rich plasma (PRP) assay. Pharmacokinetic and physiochemical properties were optimized through modifications at the 4-position ring terminal nitrogen piperazine ring, leading compound...
<p>Supplementary Figure S3. Kaplan-Meier analysis of an additional cohort 27 patients with oligometastatic mCRPC, stratified by <i>AR</i> enhancer amplification status in plasma cell-free DNA. (A) Progression-free survival, (B) radiographic progression-free and (C) overall survival. p values were calculated the log-rank test.</p>
<p>Supplementary Figure S1. Genomic landscape of metastatic castration-resistant prostate cancer (mCRPC) samples profiled using EnhanceAR-Seq. EnhanceAR-Seq, Enhancer and neighboring loci Androgen Receptor Sequencing.</p>
<p>Supplementary Figure S9. Cell-free DNA methylation analysis of differentially accessible transcription factor binding sites. The box and whisker plots summarize levels in plasma cfDNA from <i>AR</i>/enhancer altered versus wild-type mCRPC patients after z-score transformation the 10,000 TF sites corresponding to each top 20 TFs that are (A) most (B) least lethal high-risk patients. p values were calculated by Mann-Whitney U test. cfDNA, cell-free DNA; mCRPC, metastatic...
<p>Supplementary Figure S11. Cell-free DNA methylation levels of the top 10 least stem-like signature genes in plasma. The box and whisker plots summarize promoter rates for plasma cfDNA from <i>AR</i>/enhancer altered versus wild-type mCRPC patients. p values were calculated by Student’s t test. cfDNA, cell-free DNA; mCRPC, metastatic castration-resistant prostate cancer; TF, transcription factor.</p>
<p>Supplementary Figure S2. Kaplan-Meier analysis based on plasma collected prior to first-line androgen receptor-signaling inhibitor (ARSI) treatment according (A,B) Androgen receptor (<i>AR</i>) gene body status and (C,D) <i>AR</i> enhancer region in 63 patients with metastatic castration-resistant prostate cancer (mCRPC). p values were calculated by the log-rank test hazard ratios (HRs) Mantel-Haenszel method.</p>
<p>Supplementary Figure S7. Distribution of differentially methylated regions in mCRPC plasma cell-free DNA. (A) hypomethylated and hypermethylated genic DMRs pre-treatment cfDNA <i>AR</i>/enhancer altered lethal (compared to wild-type mCRPC). (B) Genomic annotation based on their location the genome. (C) Top 50 found from patients cfDNA, DNA; CDS, coding sequence; DMRs, regions; mCRPC, metastatic castration-resistant prostate cancer; UTR, untranslated region.</p>
<p>Supplementary Figure S8. Transcription factor analysis in localized prostate cancer versus blood. Log2 fold change of the 20 TFs with most accessible and least binding sites plasma cell-free DNA (see Fig. 4E, Table S12 S13) adenocarcinoma tumors from TCGA (n = 496) blood samples GTEX 337) (Methods). p value was calculated by Student’s t test. GTEX, Genotype-Tissue Expression project; TCGA, The Cancer Atlas Genome TF, transcription factor.</p>
<p>Supplementary Figure S5. Kaplan-Meier survival analysis based on plasma collected prior to first-line androgen receptor-signaling inhibitor (ARSI) treatment in 63 mCRPC patients according (A,B) <i>PTEN</i> copy number loss status cfDNA, (C,D) or mutation and (E,F) alteration <i>AR</i>/Enhancer cfDNA. p values were calculated by the log-rank test hazard ratios (HRs) Mantel-Haenszel method. cell-free DNA; mCRPC; metastatic castration-resistant prostate cancer.</p>
<p>Supplementary Figure S6. Kaplan–Meier survival analysis of the 43-patient mCRPC cohort that also underwent genome-wide EM-seq, according to (A,B) <i>AR</i>/enhancer alteration status and (C,D) median-split ichorCNA-based median tumor fraction. p values were calculated by log-rank test hazard ratios (HRs) Mantel-Haenszel method. cfDNA, cell-free DNA; mCRPC; metastatic castration-resistant prostate cancer.</p>