A5067588413- Glioma Diagnosis and Treatment
- Brain Metastases and Treatment
- Radiopharmaceutical Chemistry and Applications
- CNS Lymphoma Diagnosis and Treatment
- Lung Cancer Research Studies
- Cancer, Hypoxia, and Metabolism
- Cancer Treatment and Pharmacology
- Radiomics and Machine Learning in Medical Imaging
- Meningioma and schwannoma management
- Ferroptosis and cancer prognosis
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Immune cells in cancer
- Cancer Research and Treatments
- Histone Deacetylase Inhibitors Research
- Renal and related cancers
- Neuroblastoma Research and Treatments
- Bacterial Infections and Vaccines
- Spine and Intervertebral Disc Pathology
- Management of metastatic bone disease
- Cell Adhesion Molecules Research
- Vascular Malformations Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
Penn State Milton S. Hershey Medical Center
2015-2025
Pennsylvania State University
2006-2024
National Cancer Institute
2014
University of Virginia
2008-2012
Cancer Institute (WIA)
2006-2009
UCLA Medical Center
2009
Neurological Surgery
2009
Abstract Tumor necrosis commonly exists and predicts poor prognoses in many cancers. Although it is thought to result from chronic ischemia, the underlying nature mechanisms driving involved cell death remain obscure. Here, we show that glioblastoma (GBM) involves neutrophil-triggered ferroptosis. In a hyperactivated transcriptional coactivator with PDZ-binding motif-driven GBM mouse model, neutrophils coincide temporally spatially. Neutrophil depletion dampens necrosis. Neutrophils isolated...
BackgroundMedian survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated long-term remain poorly defined.MethodsEuropean Organization Research Treatment Cancer (EORTC) 1419 (ETERNITY) is a registry study supported by Brain Tumor Funders Collaborative US EORTC Group. Patients surviving at least years from diagnosis were identified 24 sites Europe, US, Australia. In isocitrate...
Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors.In randomized trial (NCT03632135), assay, personalized approach selecting most effective treatment from FDA-approved chemotherapies, improves survival rGBM (2016 WHO classification) over physician-chosen chemotherapy. In...
BACKGROUND AND OBJECTIVES: Administration of intraventricular chemotherapy through Ommaya reservoir is indicated for certain forms leptomeningeal disease. However, ventricular reservoirs carry a substantial risk infection. The conventional approach to managing reservoir-associated infections involves removal the and systemic antibiotic therapy, but this strategy necessitates additional procedures remove subsequently replace device. We evaluated success rate standardized, multimodal medical...
In 35 adolescent females (17 +/- 2 years) with polycystic ovary syndrome (PCOS), median body mass index (BMI) 30.8 kg/m2, we assessed effeicacy of metformin-diet for 1 year reduction weight, insulin, HOMA insulin resistance (IR), cholesterol, triglycerides, and resumption regular menses.Calories (26% protein, 44% carbohydrate) were targeted to 1,500-1,800/day if BMI was <25 or 1,200-1,500/day > = 25, along 2,550 mg metformin.Median weight fell from 82.7 79.1 kg (p 0.009), 16.7 13.3 microU/ml...
Abstract We describe a patient in remission from acute lymphoblastic leukemia who developed painless common peroneal neuropathy. Magnetic resonance imaging (MRI) revealed nerve thickening and enhancement, while positron emission tomography (PET) scan demonstrated increased fluorodeoxyglucose uptake large segment of the neurovascular bundle, suggesting peripheral infiltration. Both findings resolved following treatment with chemotherapy that crossed blood–nerve barrier. In selected patients...
Tumor necrosis is a poor prognostic marker in glioblastoma (GBM) and variety of other solid cancers. Accumulating evidence supports that could facilitate tumor progression resistance to therapeutics. GBM typically first detected by magnetic resonance imaging (MRI), after prominent has already formed. Therefore, radiological appearances early formation the temporal-spatial development alongside remain poorly understood. This knowledge gap leads lack reliable radiographic diagnostic/prognostic...
Abstract Pamiparib, an investigational, selective PARP1/2 inhibitor that has demonstrated potent PARP trapping and ability to cross the blood-brain barrier, showed synergistic cytotoxicity with TMZ preclinically. We report updated safety antitumor effects from a phase 1b/2 study of pamiparib + RT and/or in patients newly diagnosed or R/R GBM (SNO 2018, ACTR-30). The dose-escalation/expansion 3 arms: Arm A, (2, 4, 6 weeks) unmethylated MGMT promoter (unmethylated-GBM); B, (6 increasing dosed...
Triple-negative breast cancer (TNBC) is the most aggressive subtype with high metastasis and mortality rates. Given lack of actionable targets such as ER HER2, TNBC still remains an unmet therapeutic challenge. Despite harboring CDK4/6 expression levels, efficacy inhibition in has been limited due to emergence resistance. The resistance mainly mediated by RB1 inactivation. Since our aim overcome inhibition, this study, we primarily used cell lines that do not express RB1. Following a...
Abstract WT2725 is a Wilms’ tumor gene 1 (WT1)-derived-oligopeptide vaccine designed to induce WT1-specific cytotoxic T-lymphocytes against WT1 + tumors in human leukocyte antigen (HLA)-A*0201 and/or HLA-A*0206 patients. Here, we report the results of phase I study WT2725. In this I, open-label, dose-escalation and expansion two-part study, dosing emulsion was administered as monotherapy patients with advanced malignancies known overexpress WT1, including glioblastoma. part 1, 44 were...
2021 Background: Proteasome inhibition sensitizes glioma cells to TMZ and RT, providing a novel therapeutic strategy for GBM. MRZ, an irreversible, brain-penetrant, pan-proteasome inhibitor with anti-glioma activity was combined standard TMZ/RT → in newly diagnosed GBM (NCT02903069), determine the recommended dose (RD). The primary endpoint of this expanded phase 1 trial toxicity, secondary OS. Methods: Patients were enrolled separate cohorts (TMZ/RT+MRZ→TMZ+MRZ, N=15; TMZ/RT→TMZ+MRZ, N=18)...
We conducted a systematic review and meta-analysis to investigate the role of vascular endothelial growth factor (VEGF) inhibitors immune checkpoint (ICIs) in preventing development brain metastases (BMs).We searched MEDLINE, Embase, Cochrane Database, Google Scholar between January 1, 2000, June 2020. Included studies were randomized controlled trials (RCTs) adults with systemic cancer that reported incidence BMs treated without VEGF inhibitors, as well observational ICIs (no RCTs addressed...
2066 Background: WT2725 is a Wilms’ tumor (WT1)-derived-oligopeptide vaccine intended to induce WT1 specific cytotoxic T-lymphocytes against positive tumors in HLA-A*0201+ or HLA-A*0206+. This first human study of was conducted evaluate the safety, tolerability, and efficacy. Methods: Subjects with progressive recurrent glioblastoma (GBM), acute myeloid leukemia (AML) (patients morphologic remission minimal residual disease determined by RT-PCR were allowed), non-small cell lung cancer...
e14083 Background: Proteasome inhibition sensitizes glioma cells to TMZ and RT, providing a novel therapeutic strategy for ndGBM. MRZ, an irreversible, brain-penetrant, pan-proteasome inhibitor with anti-glioma preclinical activity was combined standard-of-care (SOC) TMZ/RT in ndGBM (NCT02903069), determine the recommended dose (RD). Methods: Patients enrolled separate concomitant (TMZ/RT+MRZ) adjuvant (TMZ+MRZ) cohorts dose-escalation (3+3 design, MRZ at 0.55, 0.7, 0.8, 1.0 mg/m2), followed...
Abstract Necrosis is commonly found in various solid tumors and predicts worse outcome. Chronic ischemia can initiate tumor necrosis, however, how the damaged tissue further expands unclear. Previous studies that neutrophils associate with necrosis could contribute development glioblastoma (GBM) through transferring myeloperoxidase-containing granules into cells inducing cell ferroptosis. How neutrophilic granule transfer occurs unknown. Here, an unbiased small molecule screen, we statins...
Abstract BACKGROUND Glioblastoma (GBM) is the most common primary brain malignancy in adults. Standard of care (SOC) for suspected GBM begins with maximal safe resection followed by adjuvant radiotherapy and temozolomide, maintenance temozolomide. Imvax has utilized its Goldspire™ platform to create IGV-001, an autologous biologic-device combination product treatment newly diagnosed (ndGBM). IGV-001 consists tumor cells antisense oligonucleotide against IGF-1R mRNA (IMV-001), irradiated...
Abstract Standard of care (SOC) for ndGBM begins with maximal safe resection followed by adjuvant radiotherapy and temozolomide, maintenance temozolomide. IGV-001 is an autologous biologic-device combination immunotherapy the treatment that consists GBM tumor cells antisense oligonucleotide against IGF-1R mRNA, irradiated administered via biodiffusion chambers implanted in abdomen. In a phase 1b study, was well tolerated without unexpected adverse events subjects ndGBM. Multiple efficacy...
Abstract INTRODUCTION Hematogenous spread of brain metastases represents conventional wisdom. However, compelling physiologic evidence suggests that may reach the CNS by way CSF either via choroid plexus or directly from bone marrow. We provide clinical invasion parenchyma occurs through CSF, and we model therapeutic implications this novel hypothesis. METHODS First, assessed whether were contiguous with a space in 204 consecutive patients using pre-treatment MRI. Then, was examined for...