A5034936114- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- Autoimmune and Inflammatory Disorders Research
- Cytokine Signaling Pathways and Interactions
- Glioma Diagnosis and Treatment
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Cancer, Hypoxia, and Metabolism
- Open Education and E-Learning
- Venous Thromboembolism Diagnosis and Management
- Radiopharmaceutical Chemistry and Applications
- Nanoplatforms for cancer theranostics
- Childhood Cancer Survivors' Quality of Life
- Advanced Radiotherapy Techniques
- Atrial Fibrillation Management and Outcomes
- Immune Cell Function and Interaction
- Brain Metastases and Treatment
- Acute Lymphoblastic Leukemia research
- Medical Imaging Techniques and Applications
- Neuroblastoma Research and Treatments
- Cancer Research and Treatments
- Prostate Cancer Treatment and Research
- Phagocytosis and Immune Regulation
- Cancer Mechanisms and Therapy
- Radiation Therapy and Dosimetry
University of Colorado Health
2020-2025
The University of Texas MD Anderson Cancer Center
2018-2024
The University of Texas Health Science Center at Houston
2018-2024
Poudre Valley Hospital
2022-2024
University of Colorado Denver
2013-2023
Children's Hospital Colorado
2016-2023
University of Colorado Anschutz Medical Campus
2015-2023
Morgan Adams Foundation
2018-2023
University of Washington
2021-2022
Fudan University
2020
Despite the success of immune checkpoint blockade against melanoma, many "cold" tumors like prostate cancer remain unresponsive. We found that hypoxic zones were prevalent across preclinical and resisted T cell infiltration even in context CTLA-4 PD-1 blockade. demonstrated hypoxia-activated prodrug TH-302 reduces or eliminates hypoxia these tumors. Combination therapy with this hypoxia-prodrug cooperated to cure more than 80% transgenic adenocarcinoma mouse prostate-derived (TRAMP-derived)...
Treatment of acute lymphoblastic leukemia (ALL) continues to advance, as evidenced by the improved risk stratification patients and development newer treatment options. Identification ALL subtypes based on immunophenotyping cytogenetic molecular markers has resulted in inclusion Philadelphia-like early T-cell precursor that affect prognosis. Ikaros mutations also emerged a prognostic factor. In addition prognostication, options for with have expanded, particularly regard relapsed/refractory...
Radiotherapy (RT) of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, abscopal tumor remissions are extremely rare, and the postirradiation immune escape mechanisms in remain elusive. Here, we found that irradiated used ATR-mediated DNA repair signaling pathway to up-regulate both CD47 PD-L1, which through engagement SIRPα PD-1, respectively, prevented phagocytosis by antigen-presenting thereby limited TAA...
The prognosis for patients with newly diagnosed acute lymphoblastic leukemia (ALL) has improved the use of more intensive chemotherapy regimens, tyrosine kinase inhibitors, targeted agents, and allogeneic hematopoietic cell transplantation. However, management relapsed or refractory (R/R) ALL remains challenging is poor. NCCN Guidelines provide recommendations on standard treatment approaches based current evidence. These Insights summarize R/R highlight important updates, a summary panel's...
Immune checkpoint blockade (ICB) has demonstrated an impressive outcome in patients with metastatic melanoma, yet, durable complete response; even Ipilimumab/Nivolumab combo are under 30%. Primary and acquired resistance response to ICB is commonly due a tumor immune escape mechanism dictated by the microenvironment (TME). Macrophage Migratory Inhibition Factor (MIF) emerged as immunosuppressive factor secreted TME. We have previously that of MIF-CD74 signaling on macrophages dendritic cells...
Abstract Five-year survival for human papilloma virus-unrelated head and neck squamous cell carcinomas remain below 50%. We assessed the safety of administering combination hypofractionated stereotactic body radiation therapy with single-dose durvalumab (anti-PD-L1) neoadjuvantly ( n = 21) NCT03635164 ). The primary endpoint study was safety, which met. Secondary endpoints included radiographic, pathologic objective response; locoregional control; progression-free survival; overall survival....
Tumors that lack pre-existing immune infiltration respond poorly to T cell checkpoint blockade immunotherapy. These cancers often surround themselves with high densities of suppressive myeloid stroma while excluding immunostimulatory dendritic cells. Tumor-resident cells and selected lymphocyte populations retain expression Toll-like Receptors (TLR) sense common features pathogens activate innate immunity in response. We explored whether agonists TLR9 could augment promote tumor regression...
Abstract Purpose: Patients with human EGFR2-positive (HER2+) breast cancer have a high incidence of brain metastases, and trastuzumab emtansine (T-DM1) is often employed. Stereotactic radiosurgery (SRS) frequently utilized, case series report increased toxicity combination SRS T-DM1. We provide an update our experience T-DM1 evaluating risk clinically significant radionecrosis (CSRN) propose mechanism for this toxicity. Experimental Design: who were ≤45 years regardless HER2 status or had...
Abstract Despite the clinical success of T-cell checkpoint blockade, most patients with cancer still fail to have durable responses immunotherapy. The molecular mechanisms driving blockade resistance, whether preexisting or evolved, remain unclear. To address this critical knowledge gap, we treated B16 melanoma combination CTLA-4, PD-1, and PD-L1 a Flt3 ligand vaccine (≥75% curative), isolated tumors resistant therapy, serially passaged them in vivo same treatment regimen until they...
Evofosfamide (TH-302) is a clinical-stage hypoxia-activated prodrug of DNA-crosslinking nitrogen mustard that has potential utility for human papillomavirus (HPV) negative head and neck squamous cell carcinoma (HNSCC), in which tumor hypoxia limits treatment outcome. We report the preclinical efficacy, target engagement, preliminary predictive biomarkers initial clinical activity evofosfamide HPV-negative HNSCC. was assessed 22 genomically characterized lines 7 line–derived xenograft (CDX),...
466 Background: Recent data support use of perioperative FLOT (5-FU/leucovorin/oxaliplatin/docetaxel) chemotherapy over pre-operative chemoradiation (CRT) for patients with resectable esophageal/GEJ adenocarcinoma limited studies evaluating combined FLOT/CRT. This prospective phase II study (NCT04028167) evaluated a neoadjuvant approach followed by CRT (EAC). Methods: Operable cT1-2 N1-2 or cT3-4N any4 Nany non-metastatic EAC were eligible. Neoadjuvant treatment consisted x 3 cycles...
Abstract Lack of robust activation Stimulator Interferon Genes (STING) pathway and subsequent induction type I IFN responses is considered a barrier to antitumor immunity in acute myeloid leukemia (AML). Using common human AML cell lines as vitro tools evaluate the efficacy novel STING agonists, we found most be poor producers IFNs upon exposure extremely potent suggesting cell-intrinsic suppression signaling may occur. We observed unexpected patterns response that did not correlate with...
Iterative reconstruction (IR) techniques are susceptible to contrast-dependent spatial resolution, limiting overall radiation dose reduction potential. Deep learning image (DLIR) may mitigate this limitation.
Abstract Background As a large number of Community Health Service (CHS) centers in China face the majority patients with non-valvular atrial fibrillation (NVAF), primary care physicians (PCPs) play role prevention embolization. Therefore, an awareness anticoagulant management NVAF must be brought into focus among PCPs China. This study investigated PCPs’ knowledge, attitudes, and practices toward therapy NVAF, to help them understand their shortcomings regarding oral (OAC) preventing Method...
We previously showed that ablation of tumor hypoxia can sensitize tumors to immune checkpoint blockade (ICB). Here, we used a Kras+/G12DTP53+/R172HPdx1-Cre (KPC) derived model pancreatic adenocarcinoma (PDAC) examine the response and adaptive resistance mechanisms involved in two established methods hypoxia-reducing therapy: hypoxia-activated prodrug TH-302 vascular endothelial growth factor receptor 2 (VEGFR-2) blockade. The combination both modalities normalized vasculature, increased DNA...