A5086095044- Glioma Diagnosis and Treatment
- Autophagy in Disease and Therapy
- Cancer Mechanisms and Therapy
- MicroRNA in disease regulation
- Ferroptosis and cancer prognosis
- Immune cells in cancer
- Melanoma and MAPK Pathways
- Neuroblastoma Research and Treatments
- PARP inhibition in cancer therapy
- Cancer Immunotherapy and Biomarkers
- Nuclear Receptors and Signaling
- Neurofibromatosis and Schwannoma Cases
- Protein Degradation and Inhibitors
- Brain Metastases and Treatment
- Cancer, Hypoxia, and Metabolism
- Computational Drug Discovery Methods
- Cannabis and Cannabinoid Research
- Chromatin Remodeling and Cancer
- Childhood Cancer Survivors' Quality of Life
- Histone Deacetylase Inhibitors Research
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Chemokine receptors and signaling
- Allergic Rhinitis and Sensitization
- Calcium signaling and nucleotide metabolism
University of Colorado Denver
2016-2025
Morgan Adams Foundation
2016-2025
Children's Hospital Colorado
2016-2025
Center for Cancer and Blood Disorders
2012-2025
University of Colorado Anschutz Medical Campus
2015-2025
University of Colorado System
2024
VA Puget Sound Health Care System
2024
University of Washington
2024
University at Buffalo, State University of New York
2024
Brigham and Women's Hospital
2024
Abstract Autophagy inhibition is a potential therapeutic strategy in cancer, but it unknown which tumors will benefit. The BRAFV600E mutation has been identified as important pediatric central nervous system (CNS) and known to affect autophagy other tumor types. We evaluated CNS cells with found that mutant (but not wild-type) display high rates of induced autophagy, are sensitive pharmacologic genetic inhibition, synergy when the clinically used inhibitor chloroquine was combined RAF...
Autophagy is a protein and organelle degradation pathway that involved in diverse diseases, including cancer. Recent evidence suggests autophagy cell survival mechanism tumor cells its inhibition, especially combination with other therapy, could be beneficial but it remains unclear if all cancer behave the same way when inhibited. We inhibited panel of breast lines found some them are dependent on for even nutrient rich conditions without any additional stress, whereas others need only...
Kinase inhibitors are effective cancer therapies, but tumors frequently develop resistance. Current strategies to circumvent resistance target the same or parallel pathways. We report here that targeting a completely different process, autophagy, can overcome multiple BRAF inhibitor mechanisms in brain tumors. BRAFV600Emutations occur many pediatric previously reported these autophagy-dependent and patient was successfully treated with autophagy chloroquine after failure of BRAFV600E...
<h3>Background</h3> Standard-of-care therapies for treating pediatric medulloblastoma have long-term side effects, even in children who are cured. One emerging modality of cancer therapy that could be equally effective without such effects would chimeric antigen receptor (CAR) T cells. Knowing human epidermal growth factor 2 (HER2) is overexpressed many medulloblastomas and has been used as a CAR target before, we sought to evaluate the efficacy more sophisticated anti-HER2 cells, well...
H3 K27M mutation was originally described in pediatric diffuse intrinsic pontine gliomas (DIPGs), but has been recently recognized to occur also adult midline gliomas, as well tumors with other morphologies, including gangliogliomas (GGs), anaplastic GGs, pilocytic astrocytomas (PAs), and posterior fossa ependymomas. In a few patients K27M;mutant these alternate longer survival reported, making grading difficult for the neuropathologist. Few series compare vs. cohorts; we report our 4-year...
Background: Clinical trials of anti-Aβ monoclonal antibodies in Alzheimer disease (AD) infer target engagement from Aβ positron emission tomography (PET) and/or fluid biomarkers such as cerebrospinal (CSF) Aβ42/40.However, these measure deposits indirectly incompletely.In contrast, postmortem neuropathologic assessments allow direct investigation treatment effects on brain and many other pathologic features.Methods: From a clinical trial dominantly inherited AD, we measured...
Disorders of the upper respiratory tract, particularly allergic rhinitis, are commonly associated with bronchial hyperresponsiveness. The latter may be due to postnasal drip or mediator chemotactic factors into lower airways that either directly alter airway reactivity cause inflammation. aim this study was compare effect an identical dose nasal corticosteroid administration on hyperresponsiveness in patients rhinitis. Eleven were studied. All them judged atopic basis positive skin tests...
Ependymoma (EPN) in childhood is a brain tumor with substantial mortality. Inflammatory response has been identified as molecular signature of high-risk Group A EPN. To better understand the biology this phenotype and aid therapeutic development, transcriptomic data from B EPN patient samples, additional malignant normal data, were analyzed to identify mechanism underlying inflammation. Enrichment IL6 STAT3 pathway genes found distinguish other tumors, implicating an activation mechanism....
Adamantinomatous craniopharyngioma (ACP) makes up between 6-8% of pediatric brain tumors and is the most common tumor arising in sellar/suprasellar region brain. The 10-year survival for patients diagnosed with ranges 64-92%, but complicating factors such as location, cyst formation, potential hypothalamic infiltration cause significant morbidity this population. There are a number therapeutic options children ACP, including surgery, radiation, directed therapies interferon bleomycin....
Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and sequencing on 32 RIG tumors in vitro drug screen two cell lines. report that based methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, Ch. 13q 14q loss; focal PDGFRA CDK4 gain CDKN2A BCOR loss. Transcriptomically,...
Abstract Background Total body irradiation (TBI) is an important component of hematopoietic stem cell transplant (SCT) for pediatric malignancies. With increasing survival rates, late effects SCT become more important. Younger children may be at particular risk radiation and SCT. Methods We retrospectively reviewed outcomes less than 3 years age who received TBI as part their preparative regimen Children's Hospital Colorado. Clinical information including the date last follow‐up, most recent...
Brainstem gangliogliomas (GGs), often cannot be resected, have a much poorer prognosis than those located in more common supratentorial sites and may benefit from novel therapeutic approaches. Therapeutically targetable BRAF c.1799T>A (p.V600E) (BRAF(V600E) ) mutations are harbored roughly 50% of collective GGs taken all anatomical sites. Large numbers pediatric brainstem GGs, however, not been specifically assessed anatomic-and age-restricted assessment genetic biological factors becoming...
A desperate need for novel therapies in pediatric ependymoma (EPN) exists, as chemotherapy remains ineffective and radiotherapy often fails. EPN have significant infiltration of immune cells, which correlates with outcome. Immune checkpoint inhibitors provide an avenue new treatments. This study characterizes tumor-infiltrating cells aims at predicting candidates clinical trials using targeting PD-L1/PD-1 (programmed death ligand 1/programmed 1).The transcriptomic profiles the primary cohort...
Abstract Background The use of next‐generation sequencing for fusion identification is being increasingly applied and aids our understanding tumor biology. Some fusions are responsive to approved targeted agents, while others have future potential therapeutic targeting. Although some pediatric central nervous system tumors may be cured with surgery alone, many require adjuvant therapy associated acute long‐term toxicities. Identification targetable can shift the treatment paradigm toward...
Posterior fossa molecular subtype A (PFA) ependymoma occurs in young children and is the deadliest of pediatric ependymoma. High-risk subtypes with chromosome 1q+ and/or 6q- exhibit significantly poorer outcome compared to wild-type PFA. However, 50% PFA patients relapse there a high risk gaining 1q at recurrence. We previously found constitutively active NF-κB, through loss LDOC1, led chronic IL-6 secretion an overall immunosuppressive tumor microenvironment higher subset (PFA1). In this...
OBJECTIVE Sepsis is associated with significant morbidity and mortality in pediatric hematology, oncology, transplant (PHOT) patients. This study characterized PHOT patients who developed hospital-onset sepsis more than 12 hours after admission identified risk factors for 30-day sepsis-attributable (SA) mortality. PATIENTS AND METHODS We analyzed an existing multicenter database of collected prospectively over 5 years (2017–2021) as part the Improving Pediatric Outcomes Collaborative. was...