A5025504463- Brain Metastases and Treatment
- Glioma Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Cancer-related molecular mechanisms research
- Barrier Structure and Function Studies
- Epigenetics and DNA Methylation
- Nanoplatforms for cancer theranostics
- Ultrasound and Hyperthermia Applications
- Lung Cancer Research Studies
- Connexins and lens biology
- Cancer Cells and Metastasis
- Chemical Synthesis and Analysis
- Histone Deacetylase Inhibitors Research
- Heat shock proteins research
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Bacillus and Francisella bacterial research
- Cancer-related gene regulation
- Photoacoustic and Ultrasonic Imaging
- RNA Interference and Gene Delivery
- Radiation Therapy and Dosimetry
- RNA and protein synthesis mechanisms
- Cancer Research and Treatments
- Autophagy in Disease and Therapy
- Circular RNAs in diseases
West Virginia University
2018-2023
Cleveland Clinic Lerner College of Medicine
2022-2023
University of Pittsburgh
2023
Neurological Surgery
2023
Children's Hospital of Pittsburgh
2023
University School
2023
Cleveland Clinic
2023
Case Comprehensive Cancer Center
2023
The transfer of intact mitochondria between heterogeneous cell types has been confirmed in various settings, including cancer. However, the functional implications on tumor biology are poorly understood. Here we show that is a prevalent phenomenon glioblastoma (GBM), most frequent and malignant primary brain tumor. We identified horizontal from astrocytes as mechanism enhances tumorigenesis GBM. This dependent network-forming intercellular connections GBM cells astrocytes, which facilitated...
Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors driven by populations of cancer stem cells (CSCs). However, few molecular mechanisms critical for CSC population maintenance have been exploited therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators the SOX2-enriched, therapy-resistant niche and identified WDR5 as indispensable this population. is component WRAD complex,...
Approximately 20% of all cancer patients will develop brain metastases in their lifespan. The standard care for with multiple is whole-brain radiation therapy, which disrupts the blood-brain barrier. Previous studies have shown inflammatory mediators play a role radiation-mediated increase permeability. Our goal was to determine if differential permeability post-radiation occurs between immunocompetent and immunocompromised mice.We utilized commissioned preclinical irradiator irradiate...
Highlights•Cx46-mediated cell-cell communication is essential for GBM self-renewal•A communication-based screening platform identifies clofazimine as a Cx46 inhibitor•Clofazimine targets CSCs and has little effect on non-stem tumor cells•Clofazimine treatment of tumor-bearing mice extends survival in vivoSummaryGap-junction-mediated enables cells to synchronize complex processes. We previously found that glioblastoma cancer stem (CSCs) express higher levels the gap junction protein compared...
Numerous studies have implicated changes in the Y chromosome male cancers, yet few investigated biological importance of noncoding RNA. Here we identify a group chromosome-expressed long RNA (lncRNA) that are involved non-small cell lung cancer (NSCLC) radiation sensitivity. Radiosensitive NSCLC lines demonstrated dose-dependent induction linc-SPRY3-2/3/4 following irradiation, which was not observed radioresistant lines. Cytogenetics revealed loss (LOY) Gain- and loss-of-function...
Abstract Blood-brain barrier (BBB) dysfunction occurs in cerebrovascular diseases and neurodegenerative disorders such as stroke. Opening of the BBB during a stroke has negative impact on acute outcomes. We have recently demonstrated that miR-34a regulates by targeting cytochrome c (CYC) vitro . To investigate role stroke, we purified primary endothelial cells (pCECs) from mouse brains following 1 h transient middle cerebral artery occlusion (tMCAO) measured real-time PCR to detect levels....
Breast cancer patients presenting with symptomatic brain metastases have poor prognosis, and current chemotherapeutic agents are largely ineffective. In this study, we evaluated the hypomethylating agent azacitidine (AZA) for its potential as a novel therapeutic in preclinical models of metastasis breast cancer. We used parental triple-negative MDA-MB-231 (231) cells their colonizing counterpart (231Br) to ascertain phenotypic differences response AZA. observed that 231Br higher metastatic...
Systemic drug delivery to the central nervous system is limited by presence of blood-brain barrier (BBB). Low intensity focused ultrasound (LiFUS) a non-invasive technique disrupt BBB, though there lack understanding relationship between LiFUS parameters, such as cavitation dose, time sonication, microbubble and course magnitude BBB disruption. Discrepancies in these data arise from experimentation with modified, clinically untranslatable transducers inconsistent parameters for sonication....
The blood-brain barrier is the selectively permeable vasculature of brain vital for maintaining homeostasis and neurological function. Low permeability beneficial in presence toxins pathogens blood. However, metastatic tumors, it a challenge drug delivery. Although blood-tumor slightly leaky, still not permissive enough to allow accumulation therapeutic concentrations metastases. Herein, we discuss differences between primary tumors vasculature, effects therapeutics on barrier,...
Patients with metastatic breast cancer have high and continually increasing rates of brain metastases. During the course disease, metastases can occur in up to 30% these patients. In most cases, are diagnosed after significant disease progression. The blood-tumor barrier increases difficulty treating metastasis by preventing accumulation chemotherapy within at therapeutically effective concentrations. Traditional therapies, such as surgical resection, radiotherapy, chemotherapy, poor...
Glioblastoma is the most common primary, malignant brain tumor that remains uniformly lethal in nearly all cases as a result of extreme cellular heterogeneity, treatment resistance, and recurrence. A major hurdle therapeutic delivery to tumors blood–brain barrier (BBB), which tightly regulated vascular between parenchyma systemic circulation prevents distribution otherwise beneficial chemotherapeutics central nervous system tumors. To overcome obstacle drug beyond BBB, nanoparticle...
Abstract Background Cancer metastasis and drug resistance have traditionally been studied separately, though these two lethal pathological phenomena almost always occur concurrently. Brain occurs in a large proportion of lung cancer patients (~ 30%). Once diagnosed, poor prognosis surviving typically less than 1 year due to lack treatment efficacy. Methods Human metastatic cells (PC-9-Br) were injected into the left cardiac ventricle female athymic nude mice. lesions allowed grow for 21...
B-cell acute lymphoblastic leukemia (ALL) is derived from an accumulation of malignant, immature B cells in the bone marrow and blood. Relapse due, part, to emergence tumor that are resistant front line standard chemotherapy associated with poor patient outcomes. This challenge highlights need for new treatment strategies eliminate residual chemoresistant cells. Based on use pitavastatin myeloid (AML), we evaluated its efficacy REH ALL cell be vincristine. We found inhibited proliferation...
Chemotherapy is more effective in the treatment of peripheral tumors than brain metastases, likely reflecting reduced ability chemotherapy to cross blood-brain barrier (BBB) and blood-tumor at efficacious concentrations. Recent studies demonstrate circadian regulation BBB. Thus, we predicted that optimally timed would increase anti-tumor efficacy a model metastases breast cancer (BMBC). First, characterized novel daily alterations BBB permeability commonly used chemotherapeutic,...
Abstract Approximately 50% of all brain metastasis cases originate from primary lung tumors. Whole-brain radiation therapy (WBRT) is a common treatment for patients with multiple metastases, but rarely survive longer than one year after diagnosis. Recent studies demonstrate improved outcomes combinatorial radiotherapy and immunotherapy, the optimal timing immunotherapy administration unclear. Eliciting robust immune response post-immunotherapy vital therapeutic efficacy. Our work shows that...
<p>Table S1 to S4; Figures S12</p>
Radiation dosimetry is critical in the accurate delivery and reproducibility of radiation schemes preclinical models for high translational relevance. Prior to performing any vitro or vivo experiments, specific dose output irradiator individual experimental designs must be assessed. Using an ionization chamber, electrometer, solid water setup, wide fields at isocenter can determined. a similar setup with radiochromic films place rates smaller different depths also In clonogenic survival...
Summary Gap junction-mediated cell-cell communication enables tumor cells to synchronize the execution of complex processes. Despite connexin family gap junction proteins being considered suppressors, we previously found that glioblastoma cancer stem (CSCs) express higher levels Cx46 compared non-stem cells, and this was necessary sufficient for CSC maintenance. To develop a targeting strategy, utilized point mutants disrupt specific functions coupling critical function CSCs. Based on...