A5051320936- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- interferon and immune responses
- CAR-T cell therapy research
- Virus-based gene therapy research
- Pancreatic and Hepatic Oncology Research
- Immune cells in cancer
- Cerebrovascular and Carotid Artery Diseases
- Cancer Research and Treatments
- Peptidase Inhibition and Analysis
- T-cell and B-cell Immunology
- Venous Thromboembolism Diagnosis and Management
- Diagnosis and Treatment of Venous Diseases
- Bacteriophages and microbial interactions
- RNA Interference and Gene Delivery
- Cardiovascular Health and Disease Prevention
- RNA modifications and cancer
- Respiratory viral infections research
- Acute Ischemic Stroke Management
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Intracranial Aneurysms: Treatment and Complications
- Phagocytosis and Immune Regulation
- Carcinogens and Genotoxicity Assessment
Providence Portland Medical Center
2015-2024
Providence College
2024
University Medical Center
2023
Hadassah Medical Center
2023
Cancer Institute (WIA)
2021-2023
Space Telescope Science Institute
2023
Dubbo Hospital
2022
University of Portland
2021
University of Leeds
2009-2019
Oregon Medical Research Center
2014-2018
Purpose: Antibodies specific for inhibitory checkpoints PD-1 and CTLA-4 have shown impressive results against solid tumors. This has fueled interest in novel immunotherapy combinations to affect patients who remain refractory checkpoint blockade monotherapy. However, how optimally combine with agents targeting T-cell costimulatory receptors, such as OX40, remains a critical question.Experimental Design: We utilized an anti-PD-1-refractory, orthotopically transplanted MMTV-PyMT mammary cancer...
Endovenous laser ablation (EVLA) is a minimally invasive technique for treating varicose veins due to truncal vein incompetence. This randomized trial compared EVLA with conventional surgery in patients primary saphenofemoral and great saphenous (GSV) reflux.Consecutive consenting symptomatic were 1 (stepwise withdrawal), 2 (continuous withdrawal) or (saphenofemoral ligation, GSV stripping, multiple phlebectomies). Principal outcome measures abolition of reflux improvement Aberdeen Varicose...
The anecdotal reports of promising results seen with immunotherapy and radiation in advanced malignancies have prompted several trials combining radiation. However, the ideal timing has not been clarified. Tumor bearing mice were treated 20Gy delivered only to tumor combined either anti-CTLA4 antibody or anti-OX40 agonist antibody. Immunotherapy was at a single timepoint around Surprisingly, optimal these therapies varied. Anti-CTLA4 most effective when given prior therapy, part due...
BackgroundAmong asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either stenting (CAS) endarterectomy (CEA) can restore patency and reduce long-term risks. However, from national registry data, each option causes about 1% procedural risk of disabling death. Comparison their protective effects requires large-scale randomised evidence.MethodsACST-2 is an international multicentre trial CAS versus CEA among thought to require...
Cytotoxic therapies prime adaptive immune responses to cancer by stimulating the release of tumor-associated antigens. However, tumor microenvironment into which these antigens are released is typically immunosuppressed, blunting ability initiate responses. Recently, activation DNA sensor molecule STING cyclic dinucleotides was shown stimulate infection-related inflammatory pathways in tumors. In this study, we report that activated ligands generate a powerful adjuvant activity for enhancing...
Ultrasound-guided foam sclerotherapy and endovenous laser ablation are widely used alternatives to surgery for the treatment of varicose veins, but their comparative effectiveness safety remain uncertain.
Transforming growth factor beta (TGFβ) is a multipotent immunosuppressive cytokine. TGFβ excludes immune cells from tumors, and inhibition improves the efficacy of cytotoxic therapies. Using preclinical colorectal cancer models in cell type-conditional receptor I (ALK5) knockout mice, we interrogate this mechanism. Tumor delay radiation response are unchanged animals with Treg or macrophage-specific ALK5 deletion. However, CD8αCre-ALK5flox/flox (ALK5ΔCD8) mice reject tumors high proportions,...
Pancreatic ductal adenocarcinoma (PDAC) has traditionally been thought of as an immunologically quiescent tumor type presumably because a relatively low mutational burden (TMB) and poor responses to checkpoint blockade therapy. However, many PDAC tumors exhibit T cell inflamed phenotypes. The presence tertiary lymphoid structures (TLS) recently shown be predictive response in melanomas sarcomas, are prognostic for survival PDAC. In order more comprehensively understand immunity patients with...
Background Checkpoint inhibitors targeting programmed death receptor-1 (PD-1) have been tested in the neoadjuvant setting for treatment of locoregionally advanced head and neck squamous cell carcinoma (HNSCC); however, response rates are modest. We hypothesized that adding stereotactic body radiation therapy (SBRT) to anti-PD-1 would be safe prior definitive surgical resection enhance pathological compared with historical cohorts patients HNSCC treated checkpoint inhibitor alone. Methods The...
Abstract Acquisition of full T-cell effector function and memory differentiation requires appropriate costimulatory signals, including ligation the molecule OX40 (TNFRSF4, CD134). Tumors often grow despite presence tumor-specific T cells establish an environment with weak costimulation immune suppression. Administration agonists has been shown to significantly increase survival tumor-bearing mice was dependent on both CD4 CD8 during priming. To understand how work in established tumors, we...
The tumor recurrence from residual local or micrometastatic disease remains a problem in cancer therapy. In patients with soft tissue sarcoma and the inoperable nonsmall cell lung cancer, is common significant mortality caused by subsequent emergence of metastatic disease. Thus, although aim primary therapy curative, outcome may be improved additional targeting microscopic We display murine model that surgical removal large results approximately 50% animals. Depletion CD8 T cells 100%...
Abstract Radiation therapy is a source of tumor antigen release that has the potential to serve as an endogenous vaccination event. In preclinical models radiation synergizes with checkpoint inhibitors cure tumors via CD8 T cell responses. To evaluate immune response initiated by therapy, we used range approaches block pre-existing artifact implantation. We demonstrate blocking responses at implantation blocks development tumor-resident specific population and prevents combined...
Preclinical studies have shown synergy between radiation therapy and immunotherapy. However, in almost all preclinical models, is delivered single doses or short courses of high (hypofractionated radiation). By contrast most clinical settings, as standard small daily fractions 1.8-2 Gy to achieve total 50-54 (fractionated We do not yet know the optimal dose scheduling for combination with chemotherapy immunotherapy.To address this, we analyzed effect neoadjuvant fractionated hypofractionated...
Background Foam sclerotherapy (foam) and endovenous laser ablation (EVLA) have emerged as alternative treatments to surgery for patients with varicose veins, but uncertainty exists regarding their effectiveness in the medium longer term. Objectives To assess clinical cost-effectiveness of foam, EVLA treatment veins. Design A parallel-group randomised controlled trial (RCT) without blinding, economic modelling evaluation. Setting Eleven UK specialist vascular centres. Participants Seven...
Endovenous laser ablation and ultrasound-guided foam sclerotherapy are recommended alternatives to surgery for the treatment of primary varicose veins, but their long-term comparative effectiveness remains uncertain.In a randomized, controlled trial involving 798 participants with veins at 11 centers in United Kingdom, we compared outcomes ablation, sclerotherapy, surgery. Primary 5 years were disease-specific quality life generic life, as well cost-effectiveness based on models expected...
Group B streptococci overcome neutrophils in placental membranes, inducing fetal injury and preterm labor.
Radiation therapy (RT) activates multiple immunologic effects in the tumor microenvironment (TME), with diverse dose-response relationships observed. We hypothesized that, contrast homogeneous RT, a heterogeneous RT dose would simultaneously optimize activation of immunogenic single TME, resulting more effective antitumor immune response. Using high-dose-rate brachytherapy, we treated mice bearing syngeneic tumors fraction at ranging from 2 to 30 gray. When combined dual checkpoint...