Browsing by Author "Galban, Stefanie"

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    Stereotactic Transcranial Focused Ultrasound Targeting System for Murine Brain Models
    (IEEE, 2021) Choi, Sang W.; Gerhardson, Tyler I.; Duclos, Sarah E.; Surowiec, Rachel; Scheven, Ulrich; Galban, Stefanie; Lee, Fred T., Jr.; Greve, Joan M.; Balter, James M.; Hall, Timothy L.; Xu, Zhen; Radiology and Imaging Sciences, School of Medicine
    An inexpensive, accurate focused ultrasound stereotactic targeting method guided by pre-treatment MRI images for murine brain models is presented. Uncertainty of each sub-component of the stereotactic system was analyzed. The entire system was calibrated using clot phantoms. The targeting accuracy of the system was demonstrated with an in vivo mouse glioblastoma (GBM) model. The accuracy was quantified by the absolute distance difference between the prescribed and ablated points visible on the pre- and post-treatment MR images, respectively. A pre-calibration phantom study (N= 6) resulted in an error of 0.32 ± 0.31, 0.72 ± 0.16, and 1.06 ± 0.38 mm in axial, lateral, and elevational axes, respectively. A post-calibration phantom study (N= 8) demonstrated a residual error of 0.09 ± 0.01, 0.15 ± 0.09, and 0.47 ± 0.18 mm in axial, lateral, and elevational axes, respectively. The calibrated system showed significantly reduced (p<0.05) error of 0.20 ± 0.21, 0.34 ± 0.24, and 0.28 ± 0.21 mm in axial, lateral and elevational axes, respectively in the in vivo GBM tumor-bearing mice (N= 10).
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    Transcriptomic Analysis of Diffuse Intrinsic Pontine Glioma (DIPG) Identifies a Targetable ALDH-Positive Subset of Highly Tumorigenic Cancer Stem-like Cells
    (American Association for Cancer Research, 2021) Surowiec, Rachel K.; Ferris, Sarah F.; Apfelbaum, April; Espinoza, Carlos; Mehta, Ranjit K.; Monchamp, Karamoja; Sirihorachai, Veerin R.; Bedi, Karan; Ljungman, Mats; Galban, Stefanie; Radiology and Imaging Sciences, School of Medicine
    Understanding the cancer stem cell (CSC) landscape in diffuse intrinsic pontine glioma (DIPG) is desperately needed to address treatment resistance and identify novel therapeutic approaches. Patient-derived DIPG cells demonstrated heterogeneous expression of aldehyde dehydrogenase (ALDH) and CD133 by flow cytometry. Transcriptome-level characterization identified elevated mRNA levels of MYC, E2F, DNA damage repair (DDR) genes, glycolytic metabolism, and mTOR signaling in ALDH+ compared with ALDH-, supporting a stem-like phenotype and indicating a druggable target. ALDH+ cells demonstrated increased proliferation, neurosphere formation, and initiated tumors that resulted in decreased survival when orthotopically implanted. Pharmacologic MAPK/PI3K/mTOR targeting downregulated MYC, E2F, and DDR mRNAs and reduced glycolytic metabolism. In vivo PI3K/mTOR targeting inhibited tumor growth in both flank and an ALDH+ orthotopic tumor model likely by reducing cancer stemness. In summary, we describe existence of ALDH+ DIPGs with proliferative properties due to increased metabolism, which may be regulated by the microenvironment and likely contributing to drug resistance and tumor recurrence. IMPLICATIONS: Characterization of ALDH+ DIPGs coupled with targeting MAPK/PI3K/mTOR signaling provides an impetus for molecularly targeted therapy aimed at addressing the CSC phenotype in DIPG.