A5073213708- Thyroid Cancer Diagnosis and Treatment
- S100 Proteins and Annexins
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- BRCA gene mutations in cancer
- Immunotherapy and Immune Responses
- Nutrition, Genetics, and Disease
- T-cell and B-cell Immunology
- Cancer Cells and Metastasis
- Immune Cell Function and Interaction
- Ferroptosis and cancer prognosis
- Genetic factors in colorectal cancer
- CAR-T cell therapy research
- Cell Adhesion Molecules Research
- Cancer, Stress, Anesthesia, and Immune Response
- Monoclonal and Polyclonal Antibodies Research
- Galectins and Cancer Biology
- Radiomics and Machine Learning in Medical Imaging
- Biomarkers in Disease Mechanisms
- TGF-β signaling in diseases
- HER2/EGFR in Cancer Research
- Hippo pathway signaling and YAP/TAZ
- Lymphoma Diagnosis and Treatment
- Cytokine Signaling Pathways and Interactions
- Estrogen and related hormone effects
University of Colorado Denver
2009-2024
University of Colorado Anschutz Medical Campus
2005-2024
University of Colorado Cancer Center
2010-2024
The Medical Center of Aurora
2012-2016
National Jewish Health
2007-2009
University of Colorado Health
2007
Denver Health Medical Center
2007
Mayo Clinic
2003
Mayo Clinic in Arizona
2003
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 Murine γδ T cell subsets, defined by their Vγ chain usage, have been shown in various disease models to distinct functional roles. In this study, we examined the responses of two main peripheral Vγ1+ and Vγ4+ cells, during collagen-induced arthritis (CIA), a mouse model that shares many hallmarks with human rheumatoid arthritis. We found whereas both subsets increased number, only cells became activated. Surprisingly, these appeared be Ag selected, based on preferential Vγ4/Vδ4...
Context: Ten to 30% of patients with papillary thyroid cancer (PTC) develop recurrent disease and may benefit from innovative adjuvant therapies. Immune-based therapies are under investigation treat many types cancer. The role the immune system in PTC is poorly understood. Objective: We investigated whether tumor-associated lymphocytes (TAL), absence background thyroiditis (LT), contribute severity. hypothesized that type associated would correlate parameters disease. Design: This...
Five to 10% of patients with differentiated thyroid cancers (DTC) develop invasive and/or distant metastatic disease that is marginally improved standard therapies. Prognosis poor for anaplastic cancer, a median survival 3–5 months. We suggest paradigm shift necessary in the treatment advanced cases. hypothesized T-cell response generated cancer and may be viable therapeutic target. Primary DTCs were analyzed by quantitative RT-PCR (n = 92) expression CD3, CD8, forkhead box (Fox)-P3,...
Context:Recurrent metastatic lymph node (LN) disease is common in patients with papillary thyroid cancer (PTC). Novel prognostic markers may be helpful guiding a therapeutic approach. Our previous studies revealed that immune suppression evident PTC and associated more severe disease.
Regional metastatic differentiated thyroid cancer (mDTC) provides a unique model in which to study the tumor-immune interface. These lymph node metastases persist for years, generally without progression distant metastases. Although immune system likely impedes disease progression, it is unsuccessful eliminating disease. Our previous studies revealed that programmed death-1 (PD-1)(+) T cells were enriched tumor-involved nodes (TILN). Tumor-associated leukocytes and tumor collected from...
Lenvatinib, a potent multikinase inhibitor, improves progression-free survival (PFS) in patients with radioiodine (RAI)-refractory differentiated thyroid cancer; however, most experience disease progression, warranting further therapy. We evaluated the efficacy and safety of lenvatinib plus pembrolizumab these patients.
Although the development of immune checkpoint inhibitors has transformed treatment strategies several human malignancies, research models to study immunotherapy in adrenocortical carcinoma (ACC) are lacking.To explore effect anti-PD1 on alteration milieu ACC a newly generated preclinical model and correlate with response matched patient.To characterize CU-ACC2-M2B patient-derived xenograft humanized mouse model, evaluate PD-1 inhibitor therapy, compare it CU-ACC2 patient metastatic...
Background: Despite advances in targeted kinase inhibitor development for patients with medullary thyroid cancer (MTC), most develop resistance and would benefit from alternative approaches. Immune-based therapies are now considered progressive MTC. This study is the first comprehensive assessment of immune milieu, immune-suppressive molecules, potential tumor antigens Methods: Primary and/or regionally metastatic tissues 46 MTC were screened infiltrates by using standard...
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).
6512 Background: Lenvatinib is an approved therapy for patients with RAIR DTC. While the overall response rate (ORR) high, few achieve a complete (CR) and most eventually have progressive disease (PD). Combination lenvatinib pembrolizumab being explored in many different cancers, this combination has been advanced endometrial carcinoma. Methods: Patients DTC Response Evaluation Criteria Solid Tumor (RECIST v1.1) measurable PD (<14 months (mo) prior to registration) were enrolled...
γδ T cells are a diverse population of lymphocytes that play an important role in immune regulation. The size the cell pool is tightly regulated, comprising only 1-10% total lymphoid mice and humans. We examined homeostatic regulation using model lymphopenia-induced expansion. found IL-15 and, to lesser extent, IL-7 homeostasis. Moreover, expansion was limited not by themselves but also natural killer αβ cells. Our results suggest CD8 + most potent inhibitors homeostasis exert their effect...
Abstract Mice sensitized and challenged with OVA were used to investigate the role of innate T cells in development allergic airway hyperresponsiveness (AHR). AHR, but not eosinophilic inflammation, was induced cell-deficient mice by small numbers cotransferred γδ invariant NKT cells, whereas either cell type alone effective. Only Vγ1+Vδ5+ enhanced AHR. Surprisingly, OVA-specific αβ required, revealing a pathway AHR mediated entirely cells. The data suggest that lymphocytic synergism, which...
Abstract Cancer cells present neoantigens dominantly through MHC class I (MHCI) to drive tumor rejection cytotoxic CD8+ T-cells. There is growing recognition that a subset of tumors express II (MHCII), causing antigens by TCRs CD4+ T-cells contribute the anti-tumor response. We find mouse Braf V600E -driven anaplastic thyroid cancers (ATC) respond markedly RAF + MEK inhibitors dabrafenib and trametinib (dab/tram) this associated with upregulation MhcII in cancer increased T-cell...
Background: Combination therapy with lenvatinib plus programmed death-1 (PD-1) immune checkpoint blockades (ICBs) is under investigation in many solid tumors, including thyroid cancer. Lenvatinib known to reduce angiogenesis and may overturn the immunosuppressive effects of vascular endothelial growth factor tumor microenvironment. Previous studies investigating VEGF receptor inhibition on response were performed rapidly growing models where equilibrium not established before treatment. We...
Successful application of gammadelta T cells in adoptive cell therapies depends upon our ability to maintain these vivo. Using an transfer model study lymphopenia-induced homeostatic expansion, we show that CD8(+) and NK1.1(+) subsets are differentially regulated. While have early sustained advantage following into TCRbeta(-/-)/delta(-/-) mice, proliferate slowly maintained at low numbers. The the subset could not be explained by increased bcl-2 or cytokine receptor expression but did...
Abstract Receptor transactivation, i.e., interaction between unrelated receptor systems, is a growing theme in cytokine and growth factor signaling. In this study we reveal for the first time ability of IFN-α to transactivate gp130 myeloma cells. An epidermal receptor/gp130 chimeric previously shown by us endogenous gp130, provided complementary tool underlying mechanisms cross-talk. Further analysis revealed that transactivation did not require extracellular or trans-membrane domain gp130....