Katrina K. Bakken
Mayo Clinic
PharmacodynamicsCancerInternal medicineDNA damageOncologyNeurosphereKinaseChemistryApoptosisIn vitroIn vivoMdm2GlioblastomaTemozolomideBlood–brain barrierCancer researchRadiation therapyMedicineBiologyPharmacologyDistribution (pharmacology)
43Publications
8H-index
294Citations
Publications 40
Newest
#1Danielle M. Burgenske (Mayo Clinic)H-Index: 2
#2Surabhi Talele (UMN: University of Minnesota)H-Index: 1
Last. Gautham Gampa (UMN: University of Minnesota)H-Index: 6
view all 22 authors...
BACKGROUND Glioblastoma (GBM) is an incurable disease with few approved therapeutic interventions. Radiation therapy (RT) and temozolomide (TMZ) remain the standards of care. The efficacy and optimal deployment schedule of the orally bioavailable small-molecule tumor checkpoint controller lisavanbulin alone, and in combination with, standards of care were assessed using a panel of IDH-wildtype GBM patient-derived xenografts. METHODS Mice bearing intracranial tumors received lisavanbulin +/- RT +...
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#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...
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#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
view all 13 authors...
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...
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#1Rachael A. Vaubel (Mayo Clinic)H-Index: 9
#2Ann C. Mladek (Mayo Clinic)H-Index: 19
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
view all 13 authors...
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#1Gaspar J. Kitange (Mayo Clinic)H-Index: 27
#2Danielle M. Burgenske (Mayo Clinic)H-Index: 2
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
view all 10 authors...
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#1Ishwar N. Kohale (MIT: Massachusetts Institute of Technology)H-Index: 2
Last. Forest M. White (MIT: Massachusetts Institute of Technology)H-Index: 60
view all 12 authors...
Abstract Formalin fixed paraffin embedded (FFPE) tissues are an invaluable source of clinical specimens. 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. We describe a method for quantitative analysis of pTyr signaling networks at an unprecedented sensitivity, with hundreds of sites quantified from 1-2 10-μm sections of FFPE tissue specimens. Phosphotyrosine profiles of flash fr...
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#1Ann C. Mladek Tuma (Mayo Clinic)H-Index: 1
#2Shiv K. Gupta (Mayo Clinic)H-Index: 8
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
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Robust function of the p53 tumor suppressor pathway is critical when treating with DNA-damage inducing agents such as radiation therapy (RT), which is a key component of standard care for GBM. MDM2 is an important negative regulator of p53 stability and MDM2 is amplified in approximately 14% of GBM. Based on the concept that suppression of MDM2 can reactivate p53 function and potentially have single agent or combinatorial effects, multiple MDM2 inhibitors have been developed. Here we report in v...
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#1Shiv K. Gupta (Mayo Clinic)H-Index: 8
#2Ann C. Mladek (Mayo Clinic)H-Index: 19
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
view all 11 authors...
Despite aggressive treatment that involves surgery, radiation and temozolomide therapy, a significant morbidity from glioblastoma (GBM) recurrence highlights the pressing unmet medical need to develop effective novel therapies for GBM. Murine Double Minute 2 (MDM2) is an important regulator of the p53 tumor suppressor, which promotes cell cycle arrest and apoptosis in response to DNA damage. Here we have assessed the efficacy of RG7388, a purported brain penetrant MDM2-inhibitor, alone or combin...
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#1Jianxiong Ji (Mayo Clinic)
#2Emily J. Smith (Mayo Clinic)H-Index: 1
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
view all 15 authors...
Radio-resistant properties of melanomas undermine benefit of radiation therapy (RT). DNA-dependent protein kinase (DNA-PKcs) is essential for the non-homologous end joining (NHEJ) mediated repair DNA double-strand break (DSB). We evaluated radio-sensitizing effects of M3814, a selective oral inhibitor of DNA-PKcs, in patient-derived xenografts (PDXs) of melanoma brain metastases. M3814 (≥300 nM) inhibited RT-induced (5 Gy) auto-phosphorylation of serine-2056 of DNA-PKcs in primary cultures of M1...
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