A5075734879- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- PARP inhibition in cancer therapy
- Melanoma and MAPK Pathways
- CAR-T cell therapy research
- Immune cells in cancer
- Neutropenia and Cancer Infections
- Nanoplatforms for cancer theranostics
- Barrier Structure and Function Studies
- Histone Deacetylase Inhibitors Research
- Glioma Diagnosis and Treatment
- Chemokine receptors and signaling
- Immune Cell Function and Interaction
- Lipid metabolism and disorders
- MicroRNA in disease regulation
- Abdominal Trauma and Injuries
- Cancer, Hypoxia, and Metabolism
- Drug Transport and Resistance Mechanisms
- Ionosphere and magnetosphere dynamics
- S100 Proteins and Annexins
- Liver Disease Diagnosis and Treatment
- Antioxidant Activity and Oxidative Stress
- Pancreatic and Hepatic Oncology Research
- HIV-related health complications and treatments
- Ferroptosis and cancer prognosis
University of Colorado Anschutz Medical Campus
2017-2023
University of Colorado Denver
2017-2020
University of Colorado Cancer Center
2020
BioElectronics (United States)
2018
Dalhousie University
1988
Victoria General Hospital
1988
Immune checkpoint inhibitors have improved overall survival rates for many cancers, yet the majority of patients do not respond to treatment and succumb disease progression. One tumor-related mechanism limiting efficacy immunotherapies in melanoma is recruitment expansion myeloid-derived suppressor cells (MDSCs). Therefore, targeting MDSCs combination with an attractive strategy improve response effectiveness.We tested this by designing a randomized phase II clinical trial treating advanced...
Ferroptosis is a form of programmed cell death associated with inflammation, neurodegeneration, and ischemia. Vitamin E (alpha-tocopherol) has been reported to prevent ferroptosis, but the mechanism by which this occurs controversial. To elucidate biochemical vitamin activity, we systematically investigated effects its major vitamers metabolites on lipid oxidation ferroptosis in striatal model. We found that specific endogenous metabolite E, alpha-tocopherol hydroquinone, was dramatically...
We sought to identify tumor-secreted factors that altered the frequency of MDSCs and correlated with clinical outcomes in advanced melanoma patients. focused our study on several many involved expansion mobilization MDSCs. These were identified by measuring circulating concentrations 13 cytokines growth stage IV patients (n = 55) healthy controls 22). Based these results, we hypothesized IL-6 IL-8 produced tumor cells participate recruitment together would be predictive overall survival then...
Abstract Objectives While much of the research concerning factors associated with responses to immune checkpoint inhibitors (ICIs) has focussed on contributions conventional peptide‐specific T cells, role unconventional such as mucosal‐associated invariant (MAIT) in human melanoma remains largely unknown. MAIT cells are an abundant population innate‐like expressing a semi‐invariant T‐cell receptor restricted MHC class I‐like molecule, MR1, presenting vitamin B metabolites derived from...
Abstract High-grade serous ovarian cancer is the deadliest gynecologic malignancy due to progression resistant disease. Claudin-4 classically defined as a tight junction protein and often associated with epithelial cancers. aberrantly expressed in nearly 70% of all tumors conveys worse overall prognosis. Elevated claudin-4 expression correlates increased DNA repair activity resistance damaging agents. PARP inhibitors are emerging an effective therapeutic option for patients function by...
Although the consequences of splenectomy are well understood in mice, much less is known about immunologic changes that occur following humans. We sought to characterize circulating immune cell populations patients before and after elective determine if these related postsplenectomy survival outcomes. Retrospective clinical information was collected from 95 undergoing compared with 91 pancreaticoduodenectomy (Whipple procedure). further analyzed peripheral blood five group, surgery, using...
Immunohistological staining of frozen sections normal human skin demonstrated the prescnce significant numbers mononuclear cells cxpressing novel epitopes associated with CD4‐positive suppressor‐inducer functions. The were located around superficial vessels and within basal layers epidermis hair follicles. antigen identified by various antibodies has been shown to be functionally important in induction suppressor capable abrogating B cell responses pokeweed mitogen. presence possible...
9536 Background: Myeloid-derived suppressor cells (MDSCs) are potent suppressors of antitumor immunity and commonly associated with poor outcomes in melanoma patients treated immune checkpoint inhibitors. Inducing the differentiation MDSCs using all-trans retinoic acid (ATRA) reduces MDSC frequency. This analysis seeks to assess safety efficacy combining ATRA pembrolizumab advanced patients. Methods: single arm, institution, phase I/II study (NCT03200847) enrolled 24 diagnosed stage IV...
125 Background: Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of immature immunosuppressive myeloid that expanded in tumor bearing hosts. Melanoma patients with high frequencies MDSCs have decreased overall survival and an increased risk death disease progression, as well impaired responses to ipilimumab. Targeting decease their frequency or suppressive activity may provide effective means improve the efficacy anti-cancer therapies. All-trans retinoic acid (ATRA) is...
Abstract While much of the research concerning factors associated with responses to immunotherapies focuses on contributions conventional peptide-specific T cells, role unconventional such as mucosalassociated invariant (MAIT) in human melanoma remains largely unknown. MAIT cells are innate-like expressing a semi-invariant cell receptor restricted non-classical MHC class I molecule MR1 presenting vitamin metabolites derived from bacteria. In this prospective clinical study, we sought...
Abstract Myeloid-derived suppressor cells (MDSCs) are potent suppressors of antitumor immunity and commonly associated with poor outcomes in melanoma patients treated immune checkpoint inhibitors. Inducing the differentiation MDSCs using all-trans retinoic acid (ATRA) alters their activity reduces MDSC frequency. This trial seeks to assess safety efficacy combining ATRA pembrolizumab metastatic patients. In 24 stage IV patients, treatment Q3W plus supplemental orally for three days...
<p>Supplementary figure 1. (A) Changes in other circulating cytokines. Colored box denotes the time when patients were being treated with ATRA. (B) example gating strategy for CD8+ T cell activation.</p>
<p>Supplementary figure 2. Changes in other clinical hematologic measures. Colored box denotes the time when patients were being treated with ATRA. * Denotes p < 0.05, ** 0.01, *** 0.001, **** 0.0001.</p>
<div>AbstractPurpose:<p>A phase Ib/II clinical trial was conducted to evaluate the safety and efficacy of combination all-trans retinoic acid (ATRA) with pembrolizumab in patients stage IV melanoma.</p>Patients Methods:<p>Anti–PD-1 naïve melanoma were treated plus supplemental ATRA for three days surrounding each first four infusions. The primary objective establish MTD recommended II dose (RP2D) combination. secondary objectives describe toxicity combined treatment...