A5058493119- Thyroid Cancer Diagnosis and Treatment
- Melanoma and MAPK Pathways
- S100 Proteins and Annexins
- Cancer-related Molecular Pathways
- Protease and Inhibitor Mechanisms
- Mechanisms of cancer metastasis
- Cancer Mechanisms and Therapy
- Advanced Breast Cancer Therapies
- Glutathione Transferases and Polymorphisms
- Nutrition, Genetics, and Disease
- BRCA gene mutations in cancer
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Ubiquitin and proteasome pathways
- Computational Drug Discovery Methods
- Hippo pathway signaling and YAP/TAZ
- Cell Adhesion Molecules Research
- Genetic factors in colorectal cancer
- Protein Kinase Regulation and GTPase Signaling
- Fibroblast Growth Factor Research
- Bioinformatics and Genomic Networks
- Growth Hormone and Insulin-like Growth Factors
- Chronic Myeloid Leukemia Treatments
University of Colorado Denver
2011-2024
University of Colorado Cancer Center
2011-2024
University of Colorado Anschutz Medical Campus
2011-2023
The Medical Center of Aurora
2020
University of Colorado Boulder
2003-2009
University of Colorado Health
1997-2003
Howard Hughes Medical Institute
2002-2003
University of Nebraska Medical Center
1999
Cell lines derived from human cancers provide critical tools to study disease mechanisms and develop novel therapies. Recent reports indicate that up 36% of cell are cross- contaminated.We evaluated 40 reported thyroid cancer-derived using short tandem repeat single nucleotide polymorphism array analysis.Only 23 tested have unique genetic profiles. The following groups likely derivatives the same line: BHP5-16, BHP17-10, BHP14-9, NPA87; BHP2-7, BHP10-3, BHP7-13, TPC1; KAT5, KAT10, KAT4,...
Abstract Purpose: To define the genetic landscape of advanced differentiated and anaplastic thyroid cancer (ATC) identify alterations potential diagnostic, prognostic, therapeutic significance. Experimental Design: The profiles 583 196 ATCs generated with targeted next-generation sequencing cancer-associated gene panels MSK-IMPACT FoundationOne were analyzed. Results: ATC had more per tumor, pediatric papillary fewer tumor when compared other types. DNA mismatch repair deficit activity...
Abstract Purpose: Thyroid cancer cell lines are valuable models but have been neglected in pancancer genomic studies. Moreover, their misidentification has a significant problem. We aim to provide validated dataset for thyroid researchers. Experimental Design: performed next-generation sequencing (NGS) and analyzed the transcriptome of 60 authenticated compared our findings with known defects human cancers. Results: Unsupervised transcriptomic analysis showed that 94% clustered distinctly...
There are no effective therapies for patients with poorly differentiated papillary thyroid cancer (PTC) or anaplastic (ATC), and metastasis to the bone represents a significantly worse prognosis. Src family kinases (SFKs) overexpressed activated in numerous tumor types have emerged as promising therapeutic target, especially relation metastasis. We recently showed that is cancer. therefore tested whether inhibition of dasatinib (BMS-354825) blocks growth metastasis.The effects on growth,...
The V600E mutation accounts for the vast majority of thyroid carcinoma-associated BRAF mutations.The aim was to study effects two ATP-competitive kinase inhibitors, PLX4032 and PLX4720, in carcinoma cell lines.We examined activity PLX4720 lines harboring (8505C, BCPAP, SW1736, BHT101), NRAS Q61R (HTH7), KRAS G12R (CAL62), HRAS G13R (C643), or RET/PTC1 (TPC-1) oncogenes. Normal thyrocytes (PC Cl 3) were used as control.Both compounds inhibited proliferation mutant lines, but not normal...
Adrenocortical cancer (ACC) is an orphan malignancy that results in heterogeneous clinical phenotypes and molecular genotypes. There are no curative treatments for this deadly with 35% survival at five years. Our understanding of the underlying pathobiology our ability to test novel therapeutic targets has been limited due lack preclinical models. Here, we report establishment two new ACC cell lines corresponding patient-derived xenograft (PDX) CU-ACC1 line PDX were derived from a...
Development of novel strategies in the treatment advanced thyroid cancer are needed. Our laboratory has previously identified a role for nuclear factor κB (NF-κB) signaling human cell growth, survival, and invasion. goal was to establish NF-κB on growth metastases vivo begin dissect mechanisms regulating this effect. We examined tumor formation five lines an model observed establishment two (8505C BCPAP). Inhibition by overexpression dominant-negative IκBα (mIκBα) significantly inhibited...
// Nikita Pozdeyev 1 , Minjae Yoo Ryan Mackie Rebecca E. Schweppe Aik Choon Tan 1, * Bryan R. Haugen Department of Medicine, University Colorado Cancer Center, School Aurora, CO, USA Two senior authors contributed equally to this work Correspondence to: Pozdeyev, email: nikita.pozdeyev@ucdenver.edu Keywords: database integration, drug sensitivity, pharmacogenomics, cancer, cell line Received: April 08, 2016 Accepted: May 29, Published: June 14, ABSTRACT The consistency in vitro sensitivity...
Focal adhesion kinase (FAK) and Src are overexpressed activated in many cancers have been associated with tumor progression. The role of the Src-FAK complex has not characterized papillary anaplastic thyroid cancer (PTC ATC).
Abstract Background Nuclear factor-κB (NF-κB) is constitutively activated in many cancers and plays a key role promoting cell proliferation, survival, invasion. Our understanding of NF-κB signaling thyroid cancer, however, limited. In this study, we have investigated the cancer invasion, apoptosis using selective genetic inhibition advanced lines. Results Three pharmacologic inhibitors differentially inhibited growth panel lines, suggesting that these may off-target effects. We therefore...
Advanced stages of papillary and anaplastic thyroid cancer continue to be plagued by a dismal prognosis, which is result limited effective therapies for these cancers. Due the high proportion cancers harboring mutations in MAPK pathway, pathway has become focal point therapeutic intervention cancer. Unfortunately, unlike melanoma, similar responsiveness inhibition yet observed patients. To address this issue, we have focused on targeting non-receptor tyrosine kinase, Src, others demonstrated...
Thyroid cancer is one of the deadliest endocrine cancers, and its incidence has been increasing. While mutations in BRAF are common thyroid cancer, advanced PTC patients currently lack therapeutic options targeting MAPK pathway, despite approved combination MEK1/2 inhibition for BRAF-mutant ATC, resistance often occurs. Here, we assess growth signaling responses to combined a panel cell lines. We first showed that synergistically inhibits four out six BRAF-mutant lines tested. Western...
Redifferentiation of thyroid carcinoma cells has the potential to increase efficacy radioactive iodine therapy in treatment-refractory, nonmedullary (TC), leading an improved disease outcome. Mammalian target rapamycin (mTOR) is a key regulator cell fate affecting survival and differentiation, with autophagy inflammation as prominent downstream pathways.The effects mTOR inhibition were studied for its redifferentiation human TC lines BC-PAP, FTC133, TPC1 by assessment mRNA protein expression...
Abstract There is a clear need to identify targetable drivers of resistance and potential biomarkers for salvage therapy patients with melanoma refractory the combination BRAF MEK inhibition. In this study, we performed whole-exome sequencing on BRAF-V600E–mutant patient tumors BRAF/MEK inhibition identified acquired oncogenic mutations in NRAS loss tumor suppressor gene CDKN2A. We hypothesized mechanisms were reactivation MAPK pathway activation cell-cycle pathway, which can both be...
Patients with advanced thyroid cancer, including papillary cancer and anaplastic (ATC), have low survival rates because of the lack efficient therapies available that can combat their aggressiveness. A total 90% cancers identifiable driver mutations, which often are components MAPK pathway, BRAF, RAS, RET-fusions. In addition, Src is a non-receptor tyrosine kinase overexpressed activated in we others shown clinically relevant target. We previously demonstrated combined inhibition dasatinib...
Thyroid diseases are common and highly heritable. Under the Global Biobank Meta-analysis Initiative, we performed a meta-analysis of genome-wide association studies from 19 biobanks for five thyroid diseases: cancer, benign nodular goiter, Graves' disease, lymphocytic thyroiditis, primary hypothyroidism. We analyzed genetic data ~2.9 million genomes identified 235 known 501 novel independent variants significantly linked to diseases. discovered correlations between autoimmune (r2=0.21-0.97)....
Introduction Advanced thyroid cancer, including papillary (PTC) and anaplastic cancer (ATC), are the leading causes of endocrine deaths. Thus, there is a critical need to identify novel therapeutic targets improve standard care. Focal Adhesion Kinase (FAK) overexpressed phosphorylated in drives growth, invasion, metastasis. FAK nonreceptor tyrosine kinase that autophosphorylated at 397 (Y397) response integrin or growth factor receptor signaling, resulting recruitment SRC proto-oncogene...
ERK5 is a recently characterized MAPK, which most similar to the well studied ERK1/2 subfamily but uses distinct mechanisms elicit responses. To understand specificity of signaling through versus ERK1/2, we examined global gene expression changes in response each pathway. Microarray measurements retinal pigment epithelial cells revealed 36 genes regulated by ERK5, all were novel targets for this 39 included 11 known genes. Of these genes, 19 both pathways. Inspection 17 uniquely that 14...
Cell lines are a widely used tool in cancer research. However, despite the relatively high incidence of papillary thyroid carcinoma (PTC), there only four PTC cell available for international research audience. The objective this study was to establish and characterize new that represent primary tumor biology. Surgical specimens were obtained generate lines. Short tandem repeat profiling confirm uniqueness against databases known mutations assessed using Sequenom. expression thyroid-specific...
There are limited therapy options for advanced thyroid cancer, including papillary and anaplastic cancer (PTC ATC). Focal adhesion kinase (FAK) regulates cell signaling by functioning as a scaffold kinase. Previously, we demonstrated that FAK is overexpressed activated in cells human PTC clinical specimens. However, it remains unclear whether patients with will benefit from inhibition. Therefore, the dual functions of mediating protumorigenic processes tumorigenesis were investigated....
The transcription factor B-Myb is a cell cycle-regulated phosphoprotein and potent regulator of cycle progression. Previous studies demonstrated that was phosphorylated at the onset S phase, suggesting it could be due to cyclin-dependent kinases. We identified 10 phosphorylation sites by automated peptide radiosequencing tryptic phosphopeptides derived from in vivo 32P-labeled B-Myb. Each site contained phosphoserine or phosphothreonine followed proline, this proline-directed kinase. Cyclin...