A5091653297- Glioma Diagnosis and Treatment
- Hematopoietic Stem Cell Transplantation
- Multiple Myeloma Research and Treatments
- Acute Myeloid Leukemia Research
- PARP inhibition in cancer therapy
- Acute Lymphoblastic Leukemia research
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Chronic Myeloid Leukemia Treatments
- Lymphoma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Cancer Research and Treatments
- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- Virus-based gene therapy research
- Cancer Treatment and Pharmacology
- Cancer Cells and Metastasis
- T-cell and B-cell Immunology
- Brain Metastases and Treatment
- Cancer, Hypoxia, and Metabolism
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Advanced Electron Microscopy Techniques and Applications
- Renal Transplantation Outcomes and Treatments
Washington University in St. Louis
2016-2025
University of Southern California
2014-2025
Barnes-Jewish Hospital
2020-2025
Jewish Hospital
2020-2025
Mayo Clinic
2015-2024
Neurological Surgery
2024
Amgen (United States)
2024
Mayo Clinic in Arizona
2009-2022
WinnMed
2010-2021
Heidelberg University
2017-2020
The molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) are unclear.We enrolled 84 adult AML MDS a single-institution trial identify somatic mutations and their relationships responses. Decitabine was administered at dose 20 mg per square meter body-surface area day for 10 consecutive days monthly cycles. We performed enhanced exome gene-panel sequencing 67 these serial multiple time points...
Recent studies have identified a Lys 27-to-methionine (K27M) mutation at one allele of H3F3A , the two genes encoding histone H3 variant H3.3, in 60% high-grade pediatric glioma cases. The median survival this group patients after diagnosis is ∼1 yr. Here we show that levels H3K27 di- and trimethylation (H3K27me2 H3K27me3) are reduced globally H3.3K27M patient samples due to expression mutant allele. Remarkably, also observed H3K27me3 Ezh2 (the catalytic subunit methyltransferase) chromatin...
Mechanical ventilation can injure the lung, causing edema and alveolar inflammation. Interleukin-8 (IL-8) plays an important role in this inflammatory response. We postulated that cyclic cell stretch upregulates production release of IL-8 by human epithelium absence structural damage or paracrine stimulation. To test hypothesis, epithelial cells (A549 cells) were cultured on a deformable silicoelastic membrane. When stretched 30% for up to 48 h, released 49 ± 34% more ( P < 0.001) than...
Temozolomide (TMZ)-based therapy is the standard of care for patients with glioblastoma multiforme (GBM), and resistance to this drug in GBM modulated by DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT). Expression MGMT silenced promoter methylation approximately half tumors, clinical studies have shown that elevated levels or lack associated TMZ some, but not all, tumors. In study, relationship between expression tumor response was evaluated four xenograft lines had been...
Abstract Purpose: Glioblastoma is the most frequent and lethal primary brain tumor. Development of novel therapies relies on availability relevant preclinical models. We have established a panel 96 glioblastoma patient-derived xenografts (PDX) undertaken its genomic phenotypic characterization. Experimental Design: PDXs were from glioblastoma, IDH-wildtype (n = 93), IDH-mutant 2), diffuse midline glioma, H3 K27M-mutant 1), both 60) recurrent 34) tumors. Tumor growth rates, histopathology,...
Natural killer (NK) cells are innate lymphoid that eliminate cancer cells, produce cytokines, and being investigated as a nascent cellular immunotherapy. Impaired NK cell function, expansion, persistence remain key challenges for optimal clinical translation. One promising strategy to overcome these is cytokine-induced memory-like (ML) differentiation, whereby acquire enhanced antitumor function after stimulation with interleukin-12 (IL-12), IL-15, IL-18. Here, reduced-intensity conditioning (RIC)
The treatment of relapsed/refractory multiple myeloma (MM) has evolved to include several new options. These combinations with second generation proteasome inhibitors (PI); immunomodulators, monoclonal antibodies, CAR T cells, bispecific selinexor, venetoclax, and many others. Most patients MM undergo cycles remissions relapse, therefore need lines combination therapies. Selecting options for requires consideration resistance status specific classes, patient-specific factors such as age...
We have previously described a panel of serially transplantable glioblastoma multiforme xenograft lines established by direct subcutaneous injection patient tumor tissue in the flanks nude mice. Here we report characterization four these with respect to their histopathologic, genetic, and growth properties following heterotopic-to-orthotopic (flank-to-intracranial) transfer. Cells from short-term cultures, excised flank xenografts, were harvested injected into brains mice (10(6) cells per...
Abstract Purpose: The influence of epidermal growth factor receptor (EGFR) amplification on glioblastoma patient prognosis following definitive radiotherapy has been extensively investigated in clinical studies, and yet the relationship between EGFR status radiation response remains unclear. intent current study was to address this using several EGFR-amplified xenografts an orthotopic athymic mouse model. Experimental Design: We examined effect survival nude mice with intracranial derived...
Abstract Development of clinically relevant tumor model systems for glioblastoma multiforme (GBM) is important advancement basic and translational biology. One that has gained wide acceptance in the neuro‐oncology community primary xenograft model. This entails engraftment patient specimens into flank nude mice subsequent serial passage these tumors mice. These are then used to establish short‐term explant cultures or intracranial xenografts. unit describes detailed procedures establishment,...
Abstract In the current study, we examined a panel of serially passaged glioblastoma xenografts, in context an intracranial tumor therapy response model, to identify associations between molecular characteristics and sensitivity epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib. From initial evaluation 11 distinct two erlotinib-sensitive tumors were identified, each having amplified EGFR expressing wild-type PTEN. One these expressed truncated EGFRvIII, whereas other...
Deregulation of the p16INK4a-Cdk4/6-Rb pathway is commonly detected in patients with glioblastoma multiforme (GBM) and a rational therapeutic target. Here, we characterized Mayo panel GBM xenografts, established from primary tissue samples GBM, evaluated their response to PD0332991, specific inhibitor Cdk4/6. All xenograft lines this study had disruptions pathway. In vitro evaluation using short-term explant cultures selected showed that PD0332991 effectively arrested cell cycle G1-phase...
Use of high-dose post-transplantation cyclophosphamide for graft-versus-host disease prophylaxis has expanded the use unmanipulated haploidentical hematopoietic cell transplantation. The immediate course in T cell-replete peripheral blood transplantation (haplo-HCT) is often complicated by symptoms resembling cytokine-release syndrome (CRS), previously described recipients targeted cellular therapeutics. However, we know little about incidence and impact CRS on outcomes these patients. To...
Abstract Purpose: The therapeutic benefit of temozolomide in glioblastoma multiforme (GBM) is limited by resistance. goal this study was to elucidate mechanisms resistance GBM. Experimental Design: We developed an vivo GBM model and used paired parental temozolomide-resistant tumors define the underlying development influence histone deacetylation (HDAC) inhibition. Results: Analysis resistant lines showed upregulation O6-methylguanine-DNA methyltransferase (MGMT) expression 3 5 xenografts....
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPentacarbonyliron(0) photocatalyzed hydrogenation and isomerization of olefinsMark A. Schroeder Mark S. WrightonCite this: J. Am. Chem. Soc. 1976, 98, 2, 551–558Publication Date (Print):January 1, 1976Publication History Published online1 May 2002Published inissue 1 January 1976https://doi.org/10.1021/ja00418a039RIGHTS & PERMISSIONSArticle Views845Altmetric-Citations129LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum full text...
Natural killer (NK) cells are an emerging cancer cellular therapy and potent mediators of antitumor immunity. Cytokine-induced memory-like (ML) NK is safe induces remissions in patients with acute myeloid leukemia (AML). However, the dynamic changes phenotype that occur after NK-cell transfer affect patient outcomes remain unclear. Here, we report comprehensive multidimensional correlates from ML cell-treated AML using mass cytometry. These data identify a unique vivo differentiated distinct...
Glioblastoma (GBM) is the most common primary malignant brain tumor and has a dismal prognosis. Measles virus (MV) therapy of GBM promising strategy due to preclinical efficacy, excellent clinical safety, its ability evoke antitumor pro-inflammatory responses. We hypothesized that combining anti– programmed cell death protein 1 (anti-PD-1) blockade MV can overcome immunosuppression enhance immune effector responses against GBM, thus improving therapeutic outcome. In vitro assays infection...
Sensitizing effects of poly-ADP-ribose polymerase inhibitors have been studied in several preclinical models, but a clear understanding predictive biomarkers is lacking. In this study, vivo efficacy veliparib combined with temozolomide (TMZ) was evaluated large panel glioblastoma multiforme (GBM) patient-derived xenografts (PDX) and potential were analyzed. The TMZ alone vs TMZ/veliparib compared 28 GBM PDX lines grown as orthotopic (8–10 mice per group); all tests statistical significance...
Glasdegib is a Hedgehog pathway inhibitor. This ongoing, open-label, phase 2 study (NCT01546038) evaluated glasdegib plus cytarabine/daunorubicin in patients with untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS). Patients received 100 mg orally, once daily continuous 28-day cycles from day -3, intravenous cytarabine mg/m2 on days 1-7 and daunorubicin 60 1-3. remission then consolidation therapy (2-4 of 1 g/m2 twice 1, 3, 5 each cycle), followed by...
Abstract Purpose: This open-label, multicenter, dose-finding, phase Ib study (NCT01546038) evaluated the safety, pharmacokinetics, pharmacodynamics, and clinical activity of novel Hedgehog pathway Smoothened inhibitor glasdegib (PF-04449913) in patients (N = 52) with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Experimental Design: Glasdegib 100 200 mg was administered orally, once daily 28-day cycles, combination low-dose cytarabine (arm A) decitabine B) to...