Ann C. Mladek
Mayo Clinic
CancerInternal medicineDNA repairPathologyDNA damageOncologyMolecular biologyApoptosisIn vitroIn vivoMdm2GlioblastomaTemozolomideBlood–brain barrierCancer researchRadiation therapyCell growthMedicineCell cultureBiologyPharmacologyDistribution (pharmacology)
69Publications
19H-index
1,314Citations
Publications 68
Newest
#1Begoña Giménez-Cassina López (Brigham and Women's Hospital)H-Index: 11
#2Ishwar N. Kohale (MIT: Massachusetts Institute of Technology)H-Index: 2
Last. Michael S. Regan (Brigham and Women's Hospital)H-Index: 7
view all 28 authors...
Background null Response to targeted therapy varies between patients for largely unknown reasons. Here, we developed and applied an integrative platform using mass spectrometry imaging (MSI), phosphoproteomics, and multiplexed tissue imaging for mapping drug distribution, target engagement, and adaptive response to gain insights into heterogeneous response to therapy. null Methods null Patient derived xenograft (PDX) lines of glioblastoma were treated with adavosertib, a Wee-1 inhibitor, and tis...
Source
#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 +...
Source
#1Bianca Maria Marin (Mayo Clinic)H-Index: 1
#2Kendra A Porath (Mayo Clinic)
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
view all 30 authors...
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...
Source
#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...
1 CitationsSource
#1Jithma P. Abeykoon (Mayo Clinic)H-Index: 11
#2Xiaosheng Wu (Mayo Clinic)H-Index: 18
Last. Thomas E. Witzig (Mayo Clinic)H-Index: 126
view all 30 authors...
Chromosome region maintenance protein1 (CRM1) mediates protein export from the nucleus and is a new target for anti-cancer therapeutics. Broader application of KPT-330 (selinexor), a first in class CRM1 inhibitor recently approved for relapsed multiple myeloma and diffuse large B-cell lymphoma, have been limited by substantial toxicity. We discovered that salicylates markedly enhance the anti-tumor activity of CRM1 inhibitors by extending the mechanisms of action beyond CRM1 inhibition. Using sa...
Source
#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...
Source
#1Jianxiong Ji (Mayo Clinic)
#2Emily L. Smith (Mayo Clinic)H-Index: 1
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
view all 22 authors...
Source
#1Jithma P. Abeykoon (Mayo Clinic)H-Index: 11
#2Xiaosheng Wu (Mayo Clinic)H-Index: 18
Last. Thomas E. Witzig (Mayo Clinic)H-Index: 126
view all 18 authors...
Source
#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...
Source
#1Jiajia Chen (Mayo Clinic)
#2Shiv K. Gupta (Mayo Clinic)H-Index: 14
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
view all 11 authors...
The efficacy of standard radiation therapy (RT) in glioblastoma (GBM) is limited, and there is a strong rationale to develop effective radiosensitizing agents. ATM is a key regulator of DNA damage induced by RT, and small molecule ATM inhibitors have shown radio-sensitizing effects in cancer cells, and may improve radio-sensitivity in GBM. Here, we evaluated the brain penetrant ATM inhibitor AZD1390 in combination with RT in GBM cell lines and patient derived xenografts (PDXs). AZD1390 (30 nM an...
Source