A5040618735- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Trace Elements in Health
- Heavy Metal Exposure and Toxicity
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
- Advanced Proteomics Techniques and Applications
- Cancer-related gene regulation
- Mechanisms of cancer metastasis
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Reactions
- Cancer Mechanisms and Therapy
- RNA modifications and cancer
- Crystallization and Solubility Studies
- Steroid Chemistry and Biochemistry
- Mass Spectrometry Techniques and Applications
- Oxidative Organic Chemistry Reactions
- Wnt/β-catenin signaling in development and cancer
- Cholesterol and Lipid Metabolism
- Sexuality, Behavior, and Technology
- Atherosclerosis and Cardiovascular Diseases
- Metastasis and carcinoma case studies
- RNA and protein synthesis mechanisms
Johns Hopkins Medicine
2024
Johns Hopkins University
2024
New York University
2017-2023
NYU Langone Health
2020
Georgetown University
2014-2015
Georgetown University Medical Center
2014-2015
National Institute of Standards and Technology
2013
Robert Wood Johnson University Hospital
2009
Winthrop-University Hospital
2005
University of Miami
1989-2000
New chemical inhibitors of protein-protein interactions are needed to propel advances in molecular pharmacology. Peptoids peptidomimetic oligomers with the capability inhibit by mimicking protein secondary structure motifs. Here we report silico design a macrocycle primarily composed peptoid subunits that targets β-catenin:TCF interaction. The interaction plays critical role Wnt signaling pathway which is over-activated multiple cancers, including prostate cancer. Using Rosetta suite...
PURPOSE Metastatic castration-resistant prostate cancer (mCRPC) with low androgen receptor (AR) and without neuroendocrine signaling, termed double-negative (DNPC), is increasingly prevalent in patients treated AR signaling inhibitors need of new biomarkers therapeutic targets. METHODS Candidate genes enriched DNPC were determined using differential gene expression analysis discovery validation cohorts mCRPC biopsies. Laboratory studies carried out human organoid cultures, (PCa) cell lines,...
Studies were undertaken to determine the effect of host zinc deficiency upon distribution Cd, Zn and Cu between within male rat kidney cytosol unfractionated cell pellet. In first experiment rates fed stock diets supplemented with 100 micrograms Cd/mL in drinking water for 30 days. Then Cd-treated rats controls segregated into groups, which received semipurified adequate or deficient 14 After this regimen there comparable concentrations total Cd metallothionein bound supernatant sonicated,...
The copper complex of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone) or CuKTS is reduced and dissociated upon reaction with Ehrlich cells. Titration the cells leads to specific binding metallothionein 1 displacement its complement zinc. Under conditions complete titration metallothionein, 1.25-2.5 nmol CuKTS/10(7) cells, cellular DNA synthesis rapidly inhibited but no long term effects on cell proliferation are observed. kinetics redistribution Cu Zn in culture animals were studied after...
RNA helicases impact structure and metabolism from transcription through translation, in part protein interactions with factors. However, there is limited knowledge on the role of factor influence upon helicase activity. A (RHA) a DExH-box that plays multiple roles cellular biology, some functions requiring its activity as while others scaffold. The oncogenic EWS-FLI1 requires RHA to enable Ewing sarcoma (ES) oncogenesis growth; small molecule, YK-4-279 disrupts this complex cells. Our...
A retrospective study of the records xeromammographic examinations 940 patients with invasive carcinoma breast diagnosed during an 11-year period in out-patient facility yielded four cases papillary carcinoma. In each these patients, xeromammography demonstrated multiple, round or oval, circumscribed areas density one quadrant a breast. Sonographic examination three showed lesions to be solid. Two had previously multiple benign intraductal papillomas, and patient solitary papilloma same The...
Abstract PIM1 is a serine/threonine kinase that promotes and maintains prostate tumorigenesis. While protein levels are elevated in cancer relative to local disease, the mechanisms by which contributes oncogenesis have not been fully elucidated. Here, we performed direct, unbiased chemical genetic screen identify substrates cells. The identified were involved variety of oncogenic processes, included N-Myc Downstream-Regulated Gene 1 (NDRG1), has reported roles suppressing cell invasion...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxidation of secondary alcohols with ozoneWilliam L. Waters, Anthony J. Rollin, Cindy M. Bardwell, Jeffrey A. Schneider, and Thomas W. AanerudCite this: Org. Chem. 1976, 41, 5, 889–891Publication Date (Print):March 1, 1976Publication History Published online1 May 2002Published inissue 1 March 1976https://pubs.acs.org/doi/10.1021/jo00867a033https://doi.org/10.1021/jo00867a033research-articleACS PublicationsRequest reuse permissionsArticle...
This study compared the practices of anesthesia, anesthesia critical care, surgical and medical care departments that have training programs for length time they withhold enteral feeding from intubated patients before seven scheduled procedures: 1) extubation; 2) tracheostomy; 3) abdominal surgery; 4) nonabdominal 5) magnetic resonance imaging or computerized tomography; placing patient in 6) Trendelenberg 7) prone position.One-time survey 297 United States.Eighty responded (27%). We median...
EWS-FLI1 is an oncogenic fusion protein implicated in the development of Ewing's sarcoma family tumors (ESFT). Using our previously reported lead compound 2 (YK-4-279), we designed and synthesized a focused library analogues. The functional inhibition analogues was measured by EWS-FLI1/NR0B1 reporter luciferase assay paired cell screening approach measuring effects on growth for human cells containing (TC32 TC71) control PANC1 lines devoid oncoprotein. Our data revealed that substitution...
Abstract Atherosclerosis and obesity share pathological features including inflammation mediated by innate adaptive immune cells. LXRα plays a central role in the transcription of inflammatory metabolic genes. is modulated phosphorylation at serine 196 (LXRα pS196), however, consequences pS196 hematopoietic cell precursors atherosclerosis have not been investigated. To assess importance phosphorylation, bone marrow from WT S196A mice was transplanted into Ldlr −/− mice, which were fed...
Abstract Prostate cancers adapt to androgen receptor (AR) pathway inhibitors and progress castration resistance due ongoing AR expression function. To counter this, we developed a new approach modulate the inhibit castration-resistant prostate cancer (CRPC) using multivalent peptoid conjugates (MPC) that contain multiple copies of AR-targeting ligand ethisterone attached peptidomimetic scaffold. Here, investigated antitumor effects compound MPC309, trivalent display conjugated oligomer...
Treatment for renal cell carcinoma (RCC) has changed rapidly in the past decade with widespread implementation of immune checkpoint inhibitors (ICIs) as first-line therapy metastatic disease. The presence liver metastases is a poor prognostic indicator but also potential to be target localized therapy. However, there limited knowledge on dynamics and long-term effects combining liver-directed transarterial chemoembolization (TACE) ICI We identified four patients RCC (mRCC) who were treated...
ABSTRACT PIM1 is an oncogenic serine/threonine kinase that promotes and maintains prostate tumorigenesis. To more fully understand the mechanism by which oncogenesis, we performed a chemical genetic screen to identify direct substrates in cancer cells. The identified were involved variety of processes, included N-Myc Downstream-Regulated Gene 1 (NDRG1), has reported roles suppression cell invasion metastasis. NDRG1 phosphorylated at serine 330 (pS330), level pS330 associated with high grade...
Abstract Background: EWS-FLI1 requires the protein binding of RNA Helicase A (RHA) to enable oncogenic transformation. RHA is a DExH box helicase family member. has critical roles modulating transcription, splicing and translation. also functions as scaffolding in multi-protein complexes including BRCA1, DICER, EGFR, POL2R, TOPO2. Our previous work demonstrated that YK-4-279 inhibited protein-protein interaction RHA, with led cellular apoptosis. The biochemical mechanism remained cryptic, so...
Abstract Prostate cancers adapt to androgen receptor (AR) pathway inhibitors and progress castration resistance despite the continued expression function of AR. We developed a new approach antagonize proliferative activity AR inhibit castration-resistant prostate cancer (CRPC) growth using multivalent peptoid conjugates (MPCs). Our strategy is display multiple copies antagonist, ethisterone, on scaffold. Such increases ligand’s effective local concentration, thus targeting with high affinity...
<p>Chemical structures and IC50 of the multivalent ethisterone-peptoid conjugate</p>