A5066807401- Mesenchymal stem cell research
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Nanoplatforms for cancer theranostics
- Immune cells in cancer
- Cancer-related molecular mechanisms research
- Cancer, Hypoxia, and Metabolism
- TGF-β signaling in diseases
- CAR-T cell therapy research
- Glioma Diagnosis and Treatment
- Extracellular vesicles in disease
- Chemokine receptors and signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Intracranial Aneurysms: Treatment and Complications
- Management of metastatic bone disease
- Cerebrovascular and Carotid Artery Diseases
- Lung Cancer Research Studies
- Polyomavirus and related diseases
- Pelvic and Acetabular Injuries
- Brain Metastases and Treatment
- Cancer, Stress, Anesthesia, and Immune Response
- Hematopoietic Stem Cell Transplantation
- Retinal and Optic Conditions
- Nanoparticle-Based Drug Delivery
Boston Medical Center
2020-2023
Duke University Hospital
2023
Duke University
2022
The University of Texas MD Anderson Cancer Center
2013-2020
University Medical Center
2020
Boston University
2020
Chukwuemeka Odumegwu Ojukwu University
2019
The University of Texas Health Science Center at Houston
2013-2015
Kumamoto University
2013
Exosomes can mediate a dynamic method of communication between malignancies, including those sequestered in the central nervous system and immune system. We sought to determine whether exosomes from glioblastoma (GBM)-derived stem cells (GSCs) induce immunosuppression. report that GSC-derived (GDEs) have predilection for monocytes, precursor macrophages. The GDEs traverse monocyte cytoplasm, cause reorganization actin cytoskeleton, skew monocytes toward suppresive M2 phenotype, programmed...
Abstract Although studies have suggested that bone marrow human mesenchymal stem cells (BM-hMSC) may be used as delivery vehicles for cancer therapy, it remains unclear whether BM-hMSCs are capable of targeting cells, including glioma (GSC), which the tumor-initiating responsible treatment failures. Using standard models, we identify TGF-β a tumor factor attracts via receptors (TGFβR) on BM-hMSCs. and rat GSCs, then show first time intravascularly administered home to GSC-xenografts express...
Leukemia poses a serious challenge to current therapeutic strategies. This has been attributed leukemia stem cells (LSCs), which occupy endosteal and sinusoidal niches in the bone marrow similar those of hematopoietic (HSCs). The signals from these provide viable setting for maintenance, survival, fate specifications cells. Advancements genetic engineering microscopy have enabled us critically deconstruct analyze anatomic functional characteristics reveal wealth new knowledge HSC biology, is...
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...
<h3>Background</h3> Low availability of oxygen in tumors contributes to the hostility tumor microenvironment toward immune system. However, dynamic relationship between local levels and surveillance by infiltrating T-lymphocytes (TIL) remains unclear. This situation reflects a methodological difficulty visualizing gradients living tissue manner that is suitable for spatiotemporal quantification contextual correlation with individual cell dynamics tracked typical fluorescence reporter...
OBJECTIVE Mesenchymal stem cells (MSCs) have been shown to localize gliomas after intravascular delivery. Because these home areas of tissue injury, the authors hypothesized that administration ionizing radiation (IR) tumor would enhance tropism MSCs gliomas. Additionally, they sought identify which radiation-induced factors might attract MSCs. METHODS To assess effect IR on MSC migration in vitro, transwell assays using conditioned medium (CM) from an irradiated commercially available...
INTRODUCTION: Exosomes secreted by cancer cells have pleiotropic functions, and can promote autocrine signaling to distant cells. Elucidating the mechanistic modulation of immune system these exosomes provides insight into potential biomarkers for detection, recurrence, response, identifies new therapeutic targets. METHODS: were isolated from human glioblastoma stem (GSC) fibroblasts (control) using differential centrifugation. Fluorescent-labeled co-cultured with peripheral blood...
Abstract Tissue damage contributes to initiation and modulation of an immune response. Tumor progression generally causes distress the surrounding tissue. However, how tumor-induced parenchymal regulates anti-tumor response remains be understood. We found that tumors invaded brain parenchyma compressed neurons causing increased expression neuronal chemokine CX3CL1/fractalkine in peritumoral margin. Intravital two-photon microscopy revealed perivascular recruitment monocyte-derived CD11c+...
Abstract Advances in our understanding of tumor immune biology and development cancer immunotherapies have led to improved outcomes for patients who suffer from aggressive cancers such as melanoma. Despite the clinical success checkpoint blockade, a majority still fail respond, underlying mechanisms that drive resistance remain unclear. To understand why subset tumors respond immunotherapy, we established novel murine model melanoma is fully resistant blockade. By vivo passaging...
INTRODUCTION: The brain has conventionally been considered to be immune-privileged, which detracted from the pursuit of immunotherapies for tumors. However, whether malignancies remain insulated immune system is unclear. T cell migration in tissues regulated part by chemokines often an organ-specific manner. We hypothesized that tumors are accessible surveillance, and this process a chemokine called fractalkine, highly expressed brain. METHODS: Cranial windows intravital multiphoton...
BACKGROUND: The extent of CD8+ T cell infiltration has been shown to correlate with improved survival in patients high-grade glioma. However, it is unknown how the CD8 effector cells influences gliomagenesis or progression from low- In this study we eliminated an otherwise immunocompetent model glioma their effect on initiation and malignant METHODS: We backcrossed CD8α KO mice into Ntv-a background then induced endogenous gliomas CD8α−/−/Ntv-a CD8+/+/Ntv-a using co-expression PDGFB STAT3....
Abstract The phenomenon of organ specificity in cancer metastasis has been traditionally interpreted terms the “seed and soil” hypothesis. However, role adaptive immune system this is largely unknown controversial. We found that MCA-fibrosarcoma cells formed lethal tumors lungs, but not brain thereby representing a model organ-specificity metastasis. Using model, we assessed system. In competent multi-color fluorescent reporter mice, longitudinal intravital imaging via cranial windows...
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<p>PDF file - 5585K, Double staining for GFP and TGF-β detects BM-hMSCs-GFP near tumor cells expressing in intracranial tumors.</p>
<p>PDF file - 2142K, Spheroids of human GSC lines.</p>
<p>PDF file - 1271K, Proliferation effects of knocking down TGFβRII or CD105 in BM-hMSCs.</p>
<p>PDF file - 2556K, TGFβ levels do not alter tumor vascularity or size.</p>
<p>PDF file - 1222K, The migration of BM-hMSCs toward increasing concentrations TGF-β1.</p>
<p>PDF file - 29856K, Assays of STR polymorphism using twelve unique markers in RCS, RAT2, C6, GSC001 low, high cells.</p>
<p>PDF file - 2142K, Spheroids of human GSC lines.</p>