Jann N. Sarkaria
Mayo Clinic
CancerInternal medicineDNA repairPathologyDNA damageOncologyMolecular biologyKinaseChemistryIn vivoGlioblastomaTemozolomideGliomaBlood–brain barrierCancer researchRadiation therapyCell growthMedicineCell cultureBiologyPharmacology
Publications 412
Recently, we involved the carbohydrate-binding protein Galectin-3 (Gal-3) as a druggable target for KRAS-mutant-addicted lung and pancreatic cancers. Here, using glioblastoma patient-derived stem cells (GSCs), we identify and characterize a subset of Gal-3high glioblastoma (GBM) tumors mainly within the mesenchymal subtype that are addicted to Gal-3-mediated macropinocytosis. Using both genetic and pharmacologic inhibition of Gal-3, we showed a significant decrease of GSC macropinocytosis activi...
#1Jeanette E. Eckel-Passow (Mayo Clinic)H-Index: 45
#2Gaspar J. Kitange (Mayo Clinic)H-Index: 27
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
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Background null Appropriately designed preclinical patient-derived xenograft (PDX) experiments are important to accurately inform human clinical trials. There is little experimental design guidance regarding choosing the number of PDX lines to study, and the number of mice within each PDX line. null Methods null Retrospective data from IDH-wildtype glioblastoma preclinical experiments evaluating a uniform regimen of fractionated radiation (RT), temozolomide (TMZ) chemotherapy, and concurrent RT/...
#1Bianca Maria Marin (Mayo Clinic)H-Index: 1
#2Kendra A Porath (Mayo Clinic)
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
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BACKGROUND Antibody drug conjugates (ADCs) targeting the epidermal growth factor receptor (EGFR), such as depatuxizumab mafodotin (Depatux-M), is a promising therapeutic strategy for glioblastoma (GBM) but recent clinical trials did not demonstrate a survival benefit. Understanding the mechanisms of failure for this promising strategy is critically important. METHODS PDX models were employed to study efficacy of systemic vs intracranial delivery of Depatux-M. Immunofluorescence and MALDI-MSI wer...
#1Ishwar N. Kohale (MIT: Massachusetts Institute of Technology)H-Index: 2
#2Danielle M. Burgenske (Mayo Clinic)H-Index: 2
Last. Forest M. White (MIT: Massachusetts Institute of Technology)H-Index: 60
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Human tissue samples commonly preserved as formalin-fixed paraffin-embedded (FFPE) tissues after diagnostic or surgical procedures in the clinic represent an invaluable source of clinical specimens for in-depth characterization of signaling networks to assess therapeutic options. Tyrosine phosphorylation (pTyr) plays a fundamental role in cellular processes and is commonly dysregulated in cancer but has not been studied to date in FFPE samples. Additionally, pTyr analysis that may otherwise info...
#1Walid M. Abdelmoula (Brigham and Women's Hospital)H-Index: 14
#2Sylwia A. Stopka (Brigham and Women's Hospital)H-Index: 9
Last. Nathalie Y. R. Agar (Brigham and Women's Hospital)H-Index: 31
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Motivation: Mass spectrometry imaging (MSI) provides rich biochemical information in a label-free manner and therefore holds promise to substantially impact current practice in disease diagnosis. However, the complex nature of MSI data poses computational challenges in its analysis. The complexity of the data arises from its large size, high dimensionality, and spectral non-linearity. Preprocessing, including peak picking, has been used to reduce raw data complexity, however peak picking is sens...
#1Sani H. Kizilbash (Mayo Clinic)H-Index: 10
#2Shiv K. Gupta (Mayo Clinic)H-Index: 8
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
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Tesevatinib is a potent oral brain penetrant EGFR inhibitor currently being evaluated for glioblastoma therapy. Tesevatinib distribution was assessed in wild-type (WT) and Mdr1a/b(-/-)Bcrp(-/-) triple knockout (TKO) FVB mice after dosing orally or via osmotic minipump; drug-tissue binding was assessed by rapid equilibrium dialysis. Two hours after tesevatinib dosing, brain concentrations in WT and TKO mice were 0.72 and 10.03 µg/g, respectively. Brain-to-plasma ratios (Kp) were 0.53 and 5.73, re...
#1Karishma Rajani (Mayo Clinic)H-Index: 8
#2Lucas P. Carlstrom (Mayo Clinic)H-Index: 8
Last. Terry C. Burns (Mayo Clinic)H-Index: 19
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#2Rosamaria Ruggieri (The Feinstein Institute for Medical Research)H-Index: 7
Last. Marc Symons (The Feinstein Institute for Medical Research)H-Index: 51
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BACKGROUND Glioblastoma is the most common primary brain tumor and remains uniformly fatal, highlighting the dire need for developing effective therapeutics. Significant intra- and inter-tumor heterogeneity and inadequate delivery of therapeutics across blood-brain barrier continue to be significant impediments towards developing therapies which can significantly enhance survival. We hypothesize that microRNAs have the potential to serve as effective therapeutics for glioblastoma as they modulat...
#1Jessica I. Griffith (UMN: University of Minnesota)H-Index: 1
#1Jessica Griffith (UMN: University of Minnesota)H-Index: 1
Last. William F. Elmquist (UMN: University of Minnesota)H-Index: 54
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Apparent blood–brain barrier (BBB) disruption is common in glioblastoma (GBM), but has not translated to improved drug delivery efficacy. Recently, de Gooijer et al . demonstrated that efflux transporters can have a prominent role in limiting drug delivery. These transport systems contribute to ineffective drug delivery to tumor cells in the brain.
#1Alan T. Yeo (Tufts University)H-Index: 1
#2Hyun Jung Jun (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 17
Last. Al Charest (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 13
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Focal amplification of epidermal growth factor receptor (EGFR) and its ligand-independent, constitutively active EGFRvIII mutant form are prominent oncogenic drivers in glioblastoma (GBM). The EGFRvIII gene rearrangement is considered to be an initiating event in the etiology of GBM, however, the mechanistic details of how EGFRvIII drives cellular transformation and tumor maintenance remain unclear. Here, we report that EGFRvIII demonstrates a reliance on PDGFRA co-stimulatory signaling during t...