A5022832293- Neuroblastoma Research and Treatments
- Cancer therapeutics and mechanisms
- Cancer Immunotherapy and Biomarkers
- Radiopharmaceutical Chemistry and Applications
- Glioma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Brain Metastases and Treatment
- Brain Tumor Detection and Classification
- interferon and immune responses
- PARP inhibition in cancer therapy
- T-cell and B-cell Immunology
- Ferroptosis and cancer prognosis
- Mathematical Biology Tumor Growth
- Immune cells in cancer
- Cancer, Stress, Anesthesia, and Immune Response
- Medical Imaging Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Diagnosis and Treatment
- Endometrial and Cervical Cancer Treatments
- Medical Imaging and Pathology Studies
- Ubiquitin and proteasome pathways
- Inflammatory Myopathies and Dermatomyositis
- Schizophrenia research and treatment
Children's Hospital of Philadelphia
2016-2023
Johns Hopkins University
2014-2015
Johns Hopkins Medicine
2014
Lymphocyte Activation Gene – 3 (LAG-3) is an immune checkpoint molecule that regulates both T-cell activation and homeostasis. However, the molecular mechanisms underlying LAG-3's function are generally unknown. Using a model in which LAG-3 blockade or absence reliably augmented homeostatic proliferation vivo, we found IL-2 STAT5 critical for function. Similarly, was ineffective of regulatory T-cells (Treg), suggesting important role either responsiveness conventional (Tconv) to regulation,...
Abstract Purpose: Immune responses to antigens originating in the central nervous system (CNS) are generally attenuated, as collateral damage can have devastating consequences. The significance of this finding for efficacy tumor-targeted immunotherapies is largely unknown. Experimental Design: B16 murine melanoma model was used compare cytotoxic against established tumors CNS and periphery. Cytokine analysis tissues from brain tumor–bearing mice detected elevated TGFβ secretion microglia...
[131I]meta-iodobenzylguanidine ([131I]MIBG) is a targeted radiotherapeutic administered systemically to deliver beta particle radiation in neuroblastoma. However, relapses the bone marrow are common. [211At]meta-astatobenzylguanidine ([211At] MABG) an alpha emitter with higher biological effectiveness and short path length which effectively sterilizes microscopic residual disease. Here we investigated safety antitumor activity [211At]MABG preclinical models of neuroblastoma.We defined...
Abstract Background The treatment of high‐risk neuroblastoma continues to present a formidable challenge pediatric oncology. Previous studies have shown that Bromodomain and extraterminal (BET) inhibitors can inhibit MYCN expression suppress ‐amplified in vivo. Furthermore, alterations within RAS‐MAPK (mitogen‐activated protein kinase) signaling play significant roles initiation, maintenance, relapse, mitogen‐activated extracellular signal‐regulated kinase (MEK) demonstrate efficacy subsets...
Background Neuroblastoma is a pediatric malignancy, and most tumor cells express the norepinephrine transporter (NET) enabling uptake of NET ligands. Meta-iodobenzylguanidine (MIBG) NET-specific ligand used as highly specific imaging agent targeted radiotherapeutic. Patients with neuroblastoma frequently require sedation during radiotherapy. Dexmedetomidine has been increasingly to achieve efficacious sedation. There are theoretical concerns that this selective alpha-2 adrenergic receptor...
Abstract BACKGROUND The alpha particle emitting radiotherapeutic [211At]MABG theoretically has superior radiobiological properties for anti-tumor efficacy compared to the currently used agent ([131I]MIBG). Specifically, [131I]MIBG does not target microscopic deposits due long path length of beta particles, while particles have both a short and higher linear energy transfer induce clustered double strand breaks. Here we sought define activity in preclinical models human neuroblastoma (NB)....
<p>: PD-1 blockade does not add to RT + Vaccination. Adding rLM-OVA significantly improve survival in mice with B16-OVA brain tumors. (N = 10 animals / group)</p>
<p>TGF-β blockade does not add to RT + vaccination. TGF-β with 1D11 (A) or LY2157299 (B) extend survival when combined rLM-OVA in mice B16-OVA brain tumors. (N= 10 animals / group).</p>
<p>Brain and flank tumors are of equivalent mass. Brain tumor mass was not different on day 17 when tissues were harvested for analysis. Experiment conducted x 2 with {greater than or equal to} 5 mice/group.</p>
<p>Brain tumors are more tolerogenic than flank or lung tumors. (A) Representative FACS plots from tumor draining lymph nodes of mice with B16-OVA brain, flank, (B) Summary graphs the percentage daughter cells producing IFN-γ recovered (5 mice/group).</p>
<p>B16-OVA brain tumors stimulate secretion of TGF-β1 from microglia. Cytokine concentrations in the supernatants OT-1 cells co-cultured with (A) CD11c+ APCs isolated spleen at a ratio 1:5, (B) APC tumor draining lymph nodes 1:1, (C) and CD11b+/CD45-mid microglia 1:5.</p>
<p>Tumor Morphology and Volume Upon Death. A) of tumors calculated using ex vivo MRI as described. B) Calculated brain tumor volumes at the time death determined by (N = 3 mice/group).</p>
<div>Abstract<p><b>Purpose:</b> Immune responses to antigens originating in the central nervous system (CNS) are generally attenuated, as collateral damage can have devastating consequences. The significance of this finding for efficacy tumor-targeted immunotherapies is largely unknown.</p><p><b>Experimental Design:</b> B16 murine melanoma model was used compare cytotoxic against established tumors CNS and periphery. Cytokine analysis tissues...
<div>Abstract<p><b>Purpose:</b> Immune responses to antigens originating in the central nervous system (CNS) are generally attenuated, as collateral damage can have devastating consequences. The significance of this finding for efficacy tumor-targeted immunotherapies is largely unknown.</p><p><b>Experimental Design:</b> B16 murine melanoma model was used compare cytotoxic against established tumors CNS and periphery. Cytokine analysis tissues...
<p>: PD-1 blockade does not add to RT + Vaccination. Adding rLM-OVA significantly improve survival in mice with B16-OVA brain tumors. (N = 10 animals / group)</p>
<p>TGF-β blockade does not add to RT + vaccination. TGF-β with 1D11 (A) or LY2157299 (B) extend survival when combined rLM-OVA in mice B16-OVA brain tumors. (N= 10 animals / group).</p>
<p>B16-OVA brain tumors stimulate secretion of TGF-β1 from microglia. Cytokine concentrations in the supernatants OT-1 cells co-cultured with (A) CD11c+ APCs isolated spleen at a ratio 1:5, (B) APC tumor draining lymph nodes 1:1, (C) and CD11b+/CD45-mid microglia 1:5.</p>
<p>Brain tumors are more tolerogenic than flank or lung tumors. (A) Representative FACS plots from tumor draining lymph nodes of mice with B16-OVA brain, flank, (B) Summary graphs the percentage daughter cells producing IFN-γ recovered (5 mice/group).</p>
<p>Brain and flank tumors are of equivalent mass. Brain tumor mass was not different on day 17 when tissues were harvested for analysis. Experiment conducted x 2 with {greater than or equal to} 5 mice/group.</p>
<p>Tumor Morphology and Volume Upon Death. A) of tumors calculated using ex vivo MRI as described. B) Calculated brain tumor volumes at the time death determined by (N = 3 mice/group).</p>
Supplementary Figure from Preclinical Development of [<sup>211</sup>At]meta- astatobenzylguanidine ([<sup>211</sup>At]MABG) as an Alpha Particle Radiopharmaceutical Therapy for Neuroblastoma