A5109331991- Head and Neck Cancer Studies
- Phagocytosis and Immune Regulation
- Cancer Cells and Metastasis
- Chronic Myeloid Leukemia Treatments
- Cancer, Hypoxia, and Metabolism
- 3D Printing in Biomedical Research
- Lung Cancer Treatments and Mutations
- Salivary Gland Disorders and Functions
- Chronic Lymphocytic Leukemia Research
- Salivary Gland Tumors Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- Cancer-related gene regulation
- Liver physiology and pathology
- RNA modifications and cancer
- Fibroblast Growth Factor Research
- Protein Degradation and Inhibitors
- Cancer-related molecular mechanisms research
- Mesenchymal stem cell research
- Cancer Research and Treatments
- Autophagy in Disease and Therapy
- Chemical Reactions and Isotopes
- Cancer Genomics and Diagnostics
- MicroRNA in disease regulation
- DNA Repair Mechanisms
- Advanced Radiotherapy Techniques
University of Wisconsin–Madison
2016-2025
University of Wisconsin Carbone Cancer Center
2013-2025
Laboratory of Molecular Genetics
2023
Wisconsin Institutes for Discovery
2017
Madison Group (United States)
2017
University of Iowa
2013
Purdue University West Lafayette
1996-2003
Creighton University
1997
Patients with human papillomavirus (HPV+)-associated head and neck cancer (HNC) show significantly improved survival outcome compared those HPV-negative (HPV-) tumors. Published data examining this difference offers conflicting results to date. We systematically investigated the radiation sensitivity of all available validated HPV+ HNC cell lines a series HPV- using in vitro vivo techniques. HNCs exhibited greater intrinsic (average SF2 HPV-: 0.59 vs. HPV+: 0.22; P < 0.0001), corresponding...
Cancer treatment is limited by inaccurate predictors of patient-specific therapeutic response. Therefore, some patients are exposed to unnecessary side effects and delays in starting effective therapy. A clinical tool that predicts sensitivity for individual needed.Patient-derived cancer organoids were derived across multiple histologies. The histologic characteristics, mutation profile, clonal structure, response chemotherapy radiation assessed using bright-field optical metabolic imaging...
The fatty acid derivative conjugated dienoic linoleate (CLA) has been shown to inhibit initiation and postinitiation stages of carcinogenesis in several experimental animal models. goal the present study was determine role increasing levels dietary CLA mouse skin tumor promotion elicited by 12-O-tetradecanoylphorbol-13-acetate (TPA). Mice were fed control (no CLA) diet during initiation, then switched diets containing 0.0%, 0.5%, 1.0%, or 1.5% (wt/wt) TPA. Body weights mice similar each...
Chromosome segregation during mitosis is highly regulated to ensure production of genetically identical progeny. Recurrent mitotic errors cause chromosomal instability (CIN), a hallmark tumors. The E6 and E7 oncoproteins high-risk human papillomavirus (HPV), which causes cervical, anal, head neck cancers (HNC), defects consistent with CIN in models anogenital cancers, but this has not been studied the context HNC. Here, we show that HPV16 induces specific type patient HNC tumors,...
ABSTRACT Absorption of calcium from high vegetables endogenously labeled with 45 Ca was studied in premenopausal women using a randomized cross over design. Chinese (C.) are major source calcium, but the bioavailability is unknown and likely affected by oxalic acid content. Calcium absorption vegetables, sweet potatoes, rhubarb, compared to milk at same level for calculation an index. generally reflected index (X±SEM) least C. spinach (0.257±0.0228) rhubarb (0.235±0.0233), intermediate...
Abstract Purpose: Radiation and cetuximab are therapeutics used in management of head neck squamous cell carcinoma (HNSCC). Despite clinical success with these modalities, development both intrinsic acquired resistance is an emerging problem the this disease. The purpose study was to investigate signaling receptor tyrosine kinase AXL radiation treatment. Experimental Design: To context treatment-resistant HNSCC, we patient-derived xenografts (PDXs) implanted into mice evaluated tumor...
Abstract M6620, a selective ATP-competitive inhibitor of the ATM and RAD3-related (ATR) kinase, is currently under investigation with radiation in patients non–small cell lung cancer (NSCLC) brain metastases. We evaluated DNA damage response (DDR) pathway profile NSCLC assessed radiosensitizing effects M6620 preclinical metastasis model. Mutation analysis transcriptome profiling DDR genes pathways was performed on patient samples. lines were proliferation, clonogenic survival, apoptosis,...
Several recent reports have suggested that peroxisome proliferator–activated receptors (PPARs) may be involved in the development of neoplasias different tissue types. The present study was undertaken to determine whether PPARs play a role skin physiology and tumorigenesis. In an initiation-promotion study, SENCAR mice treated topically with PPARα ligands conjugated linoleic acid 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic (Wy-14643) exhibited approximately 30% lower tumor yield...
Abstract Head and neck squamous cell carcinomas (HNSCC) are frequently altered along the PI3K/AKT/mTORC signaling axis. Despite excellent preclinical data, use of compounds targeting this pathway as monotherapy has been underwhelming in initial clinical trials, identification predictive biomarkers remains challenging. To investigate mTORC-specific inhibition, we tested catalytic mTORC (AZD8055) PI3K/mTORC (NVP-BEZ-235) inhibitors ± cetuximab a panel HNSCC lines patient-derived xenografts...
Purpose: Adenoid cystic carcinoma (ACC) is a rare cancer arising from the major or minor salivary gland tissues of head and neck. There are currently no approved systemic agents known radiosensitizers for ACC. Unlike more common neck squamous cell carcinomas that frequently harbor TP53 mutations, ACCs contain mutations at rate <5%, rendering them an attractive target MDM2 inhibition.Experimental Design: We report successful establishment detailed characterization TP53-WT ACC patient-derived...
Abstract Background: The mesenchymal transcript factors is a receptor tyrosine kinase that when dysregulated or overexpressed can stimulate oncogenesis. Alterations in MET are found 5% of non-small cell lung cancer but also head and neck cancers resistant to inhibitors targeting other oncogenic drivers. Our objective evaluate novel, camelid-derived, binding antibody as potential theranostic agent used expressing cancers. Methods: anti-MET VHH camelid antibody, 1E7-Fc, was identified from...
NUT carcinoma ("NC") is a rare but highly lethal solid tumor without an effective standard of care. NC caused by bromodomain-containing NUTM1 fusion genes, most commonly BRD4::NUTM1 . recruits p300 to acetylate H3K27 forming "megadomains" with the overexpression encapsulated oncogenes, notably MYC Akin , we hypothesized that transcriptional dysregulation would lead generation cancer specific antigens could be therapeutically actionable. Integrating genomics, immunopeptidomics, and...
Abstract Objective: The Cesium Irradiator Replacement Program (CIRP) was established in 2014 to replace radioisotope-based irradiators with non-radioactive alternatives, such as X-rays. As most dosimetry is based on 137Cs irradiators, transitioning X-ray systems has presented challenges radiobiological research. A key obstacle stems from the inaccurate assumption of dose a directly transferable constant across different irradiation types. To mitigate this issue, University Wisconsin-Madison,...
FGFRs are commonly altered in non-small cell lung cancer (NSCLC). activate multiple pathways including RAS/RAF/MAPK, PI3K/AKT, and STAT, which may play a role the cellular response to radiation. We investigated effects of combining selective FGFR 1-3 tyrosine kinase inhibitor AZD4547 with radiation line xenograft models NSCLC. NSCLC lines were assessed proliferation, clonogenic survival, apoptosis, autophagy, cycle, DNA damage signaling repair assays. In vivo xenografts IHC used confirm...
Overexpression and activation of the EGFR have been linked to poor prognosis in several human cancers. Cetuximab is a mAb against that used for treatment head neck squamous cell carcinoma (HNSCC) metastatic colorectal cancer. Unfortunately, most tumors intrinsic or will acquire resistance cetuximab during course therapy. Honokiol natural compound found bark leaves Chinese Magnolia tree established anticancer properties without appreciable toxicity. In this study, we hypothesized combining...
ErbB3 has been widely implicated in treatment resistance, but its role as a primary target is less clear. Canonically requires EGFR or ErbB2 for activation, whereas these two established targets are thought to signal independently of ErbB3. In this study, we show that essential tumor growth treatment-naive HNSCC patient-derived xenografts. This dependency occurs via ErbB3-mediated control activation and HIF1α stabilization, which require ligand neuregulin-1. Here, antibody selects population...