Gaspar J. Kitange
Mayo Clinic
GeneInternal medicineDNA repairPathologyDNA damageOncologyMolecular biologyGene knockdownDNA methylationIn vitroIn vivoGlioblastomaTemozolomideGliomaTumor suppressor geneO-6-methylguanine-DNA methyltransferaseDacarbazineMethylationCancer researchRadiation therapyMedicineCell cultureBiologyMethyltransferaseCancer cell
63Publications
27H-index
2,600Citations
Publications 59
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 +...
Source
#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
view all 7 authors...
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/...
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
#2Gaspar J. Kitange (Mayo Clinic)H-Index: 27
view all 2 authors...
Source
#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...
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
#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
#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...
Source
#1Rachael A. Vaubel (Mayo Clinic)H-Index: 9
#2Shulan Tian (Mayo Clinic)H-Index: 21
Last. Jann N. Sarkaria (Mayo Clinic)H-Index: 67
view all 34 authors...
Purpose: Glioblastoma is the most frequent and lethal primary brain tumor. Development of novel therapies relies on the availability of relevant preclinical models. We have established a panel of 96 glioblastoma patient derived xenografts (PDX) and undertaken its genomic and phenotypic characterization. Experimental Design: PDX were established from glioblastoma, IDH-wildtype (n=93), glioblastoma, IDH-mutant (n=2), diffuse midline glioma, H3 K27M-mutant (n=1), and both primary (n=60) and recurre...
32 CitationsSource
#1Bryan G. Harder (Mayo Clinic)H-Index: 3
#2Sen Peng (TGen: Translational Genomics Research Institute)H-Index: 12
Last. Nhan L. Tran (Mayo Clinic)H-Index: 53
view all 8 authors...
Temozolomide (TMZ) is the most commonly used chemotherapeutic agent used to treat glioblastoma (GBM), which causes significant DNA damage to highly proliferative cells. Our observations have added to accumulating evidence that TMZ induces stress-responsive cellular programs known to promote cell survival, including autophagy. As such, targeting these survival pathways may represent new vulnerabilities of GBM after treatment with TMZ. Using the T98G human glioma cell line, we assessed the molecul...
8 CitationsSource