A5047984092- Estrogen and related hormone effects
- Prostate Cancer Treatment and Research
- Histone Deacetylase Inhibitors Research
- Hormonal and reproductive studies
- Cancer, Lipids, and Metabolism
- Hepatocellular Carcinoma Treatment and Prognosis
- Nutrition and Health in Aging
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Cancer Immunotherapy and Biomarkers
- Cardiovascular Disease and Adiposity
- Biochemical and Molecular Research
- Sexual Differentiation and Disorders
- HER2/EGFR in Cancer Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer Treatment and Pharmacology
- PARP inhibition in cancer therapy
- Cancer, Stress, Anesthesia, and Immune Response
- HIV/AIDS drug development and treatment
- Inflammatory mediators and NSAID effects
- Adipokines, Inflammation, and Metabolic Diseases
- Pharmacogenetics and Drug Metabolism
- Radiopharmaceutical Chemistry and Applications
- Phytochemistry and Bioactivity Studies
- Muscle Physiology and Disorders
The Ohio State University
2016-2025
U-M Rogel Cancer Center
2023
University of North Carolina at Greensboro
2023
Comprehensive Blood & Cancer Center
2023
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2023
The Ohio State University Wexner Medical Center
2017-2022
Ohio University
2020
Ducks Unlimited
2016
GTx (United States)
2010-2014
Princess Margaret Cancer Centre
2011
Previous cell-penetrating peptides (CPPs) generally have low cytosolic delivery efficiencies, because of inefficient endosomal escape. In this study, a family small, amphipathic cyclic was found to be highly efficient CPPs, with efficiencies up 120% (compared 2.0% for Tat). These CPPs bind directly the plasma membrane phospholipids and enter mammalian cells via endocytosis, followed by release from endosome. Their total cellular uptake efficiency correlates positively binding affinity...
The partial agonist activity of a selective androgen receptor modulator (SARM) in the prostate was demonstrated orchidectomized rats. In current study, we characterized full S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (a structurally related SARM referred to other publications and hereafter as S-4) skeletal muscle, bone, pituitary castrated male Twelve weeks after castration, animals were treated with S-4 (3 or 10 mg/kg),...
Research progress from mainly over the last five years is described for a multidisciplinary collaborative program project directed toward discovery of potential anticancer agents broad range taxonomically defined organisms. Selected lead compounds with as new antitumor that are representative considerable structural diversity have continued to be obtained each tropical plants, terrestrial and aquatic cyanobacteria, filamentous fungi. Recently, focus has been on investigation constituents...
Androgen receptor (AR) mediates the growth of prostate cancer throughout its course development, including in abnormal splice variants (AR-SV)-driven advanced stage castration-resistant disease. AR stabilization by androgens makes it distinct from other steroid receptors, which are typically ubiquitinated and degraded proteasomes after ligand binding. Thus, targeting requires development agents that can sustainably degrade variant isoforms for effective therapy. Here we report discovery...
Abstract Despite the presence of CTLs in tumor microenvironment, majority immunogenic human colon cancer does not respond to immune checkpoint inhibitor immunotherapy, and microsatellite instable (MSI) tumors are naturally eliminated. The molecular mechanism underlying inactivity tumor-infiltrating is unknown. We report here that were present both MSI stable tumors. expression H3K9me3-specific histone methyltransferase SUV39H1 was significantly elevated carcinoma compared with normal...
Androgen receptor (AR) ligands are important for the development and function of several tissues organs. However, poor oral bioavailability, pharmacokinetic properties, cross-reactivity testosterone, coupled with side effects, place limits on its clinical use. Selective AR modulators (SARMs) elicit anabolic effects in muscle bone, sparing reproductive organs like prostate. molecular mechanisms underlying tissue selectivity remain ambiguous. We performed a variety vitro studies to compare...
Acalabrutinib (ACP-196) is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK) with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, model B-cell malignancy similar human diffuse large lymphoma (DLBCL). First, demonstrated that potently inhibited BTK activity downstream effectors CLBL1, cell line, primary cells. also proliferation CLBL1 Twenty dogs were enrolled...
The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number high-profile papers the field cancer biology. papers, which were published between 2010 and 2012, on basis citations Altmetric scores (<xref ref-type="bibr" rid="bib8">Errington et al., 2014</xref>). This Registered Report describes proposed replication plan key “Coding-Independent Regulation...
Histone deacetylase inhibitors (HDACi) have proven activity in hematologic malignancies, and their FDA approval multiple myeloma (MM) T-cell lymphoma highlights the need for further development of this drug class. We investigated AR-42, an oral pan-HDACi, a first-in-man phase 1 dose escalation clinical trial. Overall, treatment was well tolerated, no DLTs were evident, MTD defined as 40 mg dosed three times weekly weeks 28-day cycle. One patient each with MM mantle cell demonstrated disease...
Cancer cachexia exhibits decreased albumin and associates with short overall survival (OS) in patients non-small cell lung cancer (NSCLC), but whether on-treatment changes associate OS NSCLC treated immune checkpoint inhibitors (ICIs) combination chemoimmunotherapy has not been thoroughly evaluated.
Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), deadly disease with limited preventive strategies. Lifestyle interventions to decrease obesity represent potential approach prevent obesity-associated PDAC. In this study, we examined whether decreasing through physical activity (PA) and/or dietary changes could inflammation in humans and PDAC mice. Comparison of circulating inflammatory-associated cytokines subjects (overweight obese) before after PA intervention revealed...
// Mohamed Badawi 1, * , Jihye Kim Anees Dauki 1 Dhruvitkumar Sutaria 3 Tasneem Motiwala 2 Ryan Reyes Nissar Wani Shamalatha Kolli 4 Jinmai Jiang Christopher C. Coss Samson T. Jacob Mitch A. Phelps and Thomas D. Schmittgen College of Pharmacy, Medicine, The Ohio State University, Columbus, OH, USA Department Molecular Cellular Biochemistry, University Florida, Gainesville, FL, Comprehensive Cancer Center, These authors contributed equally to this work Correspondence to: Schmittgen, email:...
Abstract Owing to the marked sexual dimorphism of hepatocellular carcinoma (HCC), sex hormone receptor signaling has been implicated in numerous aspects liver cancer pathogenesis. We sought reconcile clear contribution androgen (AR) activity that established preclinical models HCC with clinical failure AR antagonists patients advanced by evaluating potential resistance mechanisms AR-targeted therapy. The locus was interrogated for resistance-causing genomic modifications using publicly...
Article13 January 2020Open Access Source DataTransparent process Overcoming resistance to anabolic SARM therapy in experimental cancer cachexia with an HDAC inhibitor Sophia G Liva Division of Pharmaceutics and Pharmacology, College Pharmacy, The Ohio State University, Columbus, OH, USA Search for more papers by this author Yu-Chou Tseng Medicinal Chemistry Pharmacognosy, Anees M Dauki Michael Sovic Trang Vu Sally E Henderson Department Veterinary Biosciences, Medicine, Yi-Chiu Kuo Jason A...
Abstract Purpose: Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors (NAMPTi) are currently in development, but may be limited as single-agent therapy due to compound-specific toxicity and cancer metabolic plasticity allowing resistance development. To potentially lower the doses of NAMPTis required for therapeutic benefit against acute myeloid leukemia (AML), we performed a genome-wide CRISPRi screen identify rational disease-specific partners novel NAMPTi, KPT-9274. Experimental...
Selective agonism of the estrogen receptor (ER) subtypes, ERα and ERβ, has historically been difficult to achieve due high degree ligand-binding domain structural similarity. Multiple efforts have focused on use classical organic scaffolds model 17β-estradiol geometry in design ERβ selective agonists, with several proceeding various stages clinical development. Carborane offer many unique advantages including potential for novel ligand/receptor interactions but remain relatively unexplored....
ABSTRACT Background Cancer cachexia is a debilitating syndrome characterized by irreversible losses in skeletal muscle mass, with or without adipose tissue. an underrecognized that impacts ~50% of all cancer patients and accounts for up to ~20% deaths. Lung remains one the deadliest cancers United States estimated 137 000 deaths year 2021 alone. highly comorbid cachexia. Pre‐clinical models are heavily relied upon study both lung cachexia; however, there need develop novel relationship...
Objectives: In rapidly proliferating cancer cells, the de novo pyrimidine synthesis pathway is highly activated and enhances tumor’s supply of nucleotides. HOSU-53 under development as an orally bioavailable, small-molecule inhibitor dihydroorotate dehydrogenase (DHODH), a mitochondrial enzyme that catalyzes rate-limiting step nucleotide biosynthesis, conversion (DHO) to orotate1. Biological testing verified efficacy in acute myeloid leukemia, multiple myeloma, small-cell lung cancer,...
Objectives: Higher catabolic clearance (CL) of immune checkpoint inhibitors (ICIs) is a biomarker for less favorable outcomes, independent drug exposure, in patients with cancer, thus leading to confounded exposure-response relationships. Patients rapid mAb CL present cancer cachexia phenotypes[1,2], though underlying mechanisms linking high CL, poor response, and are poorly understood. Our previous research demonstrates elevated ICIs can be replicated mouse models cachexia, the increased...
Abstract Aromatase inhibitors (AIs) such as anastrozole, letrozole and exemestane are used adjuvant treatment for postmenopausal women with hormone receptor-positive breast cancer. The interindividual pharmacokinetic variability seen AIs is extensive, this phenomenon may have important ramification AI-associated arthralgia, a common toxicity of which the etiology remains unclear. We speculated that hepatic uptake transporters involved in elimination play crucial role explaining pharmacologic...
Background: HOSU-53 (JBZ-001), an orally bioavailable new chemical entity, represents a highly potent dihydroorotate dehydrogenase (DHODH) inhibitor in late preclinical development for application cancer therapy. Methods: Multiple Good Laboratory Practice (GLP) and non-GLP studies were conducted mice, rats, dogs. Plasma samples of (DHO), the substrate DHODH, collected pharmacokinetic (PK) pharmacodynamic (PD) assessment modeling. Two modeling approaches utilized to understand PK/PD...