Absolute Quantification of 2‐Hydroxyglutarate on Tissue by MALDI MSI for Rapid and Precise Identification of IDH Mutations in Human Glioma

2021 ◽  
Author(s):  
Chunyan Lan ◽  
Hainan Li ◽  
Lei Wang ◽  
Jing Zhang ◽  
Xiaodong Wang ◽  
...  
Keyword(s):  
Absolute Quantification ◽  
Human Glioma ◽  
Precise Identification ◽  
Idh Mutations

scholarly journals IDH Mutations in Human Glioma

2012 ◽  
Vol 23 (3) ◽  
pp. 471-480 ◽  
Author(s):  
Won Kim ◽  
Linda M. Liau
Keyword(s):  
Human Glioma ◽  
Idh Mutations

scholarly journals NGMA-1. Quantification of IDH mutant alleles predicts outcome in diffuse gliomas

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii4-ii4
Author(s):  
Mathew Voisin ◽  
Gelareh Zadeh
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Absolute Quantification ◽  
Specific Method ◽  
Diffuse Glioma ◽  
Who Grade ◽  
Initial Surgery ◽  
Highly Sensitive ◽  
Idh Mutations ◽  
Diffuse Gliomas

Abstract Background IDH mutation is the main factor used in the prognostication of diffuse gliomas, however within IDH mutated gliomas there still remains a high variability in both tumor progression and overall survival.1 Digital droplet polymerase chain reaction (ddPCR) is one of the latest molecular amplification techniques that offers high precision in addition to the ability of absolute quantification of mutant allele copies.2 Methods A total of 102 IDH mutant diffuse glioma tumor samples ranging from WHO grade 2 to 4 were collected. This cohort includes a total of 45 paired samples collected at two distinct surgical timepoints: initial and recurrent. All samples underwent DNA extraction. A total of 5 ng of tumor DNA from each sample was analyzed using ddPCR for the detection and quantification of IDH1 R132H mutant alleles. Sanger sequencing was performed on all samples as a gold standard. Results ddPCR was highly sensitive (100%) and specific (99%) for the detection of IDH mutations. Initial tumor samples with a high number of IDH mutant copies split by median demonstrated decreased overall survival (p = 0.04) and shorter progression free survival (p = 0.024). The number of IDH mutant copies was independent of WHO grade (p = 0.6) and 1p19q codeletion status (p = 0.86). Tumor pairs that had IDH mutant copies increase at recurrence were trending but not significantly related to a decrease in remaining survival (p = 0.1). Conclusions ddPCR is a highly sensitive and specific method of detecting IDH mutations in diffuse gliomas. The number of IDH mutant copies in tumors at initial surgery can serve as an independent prognostic factor to help guide future treatment and follow-up.

Quantification of Biological Resistance: Introducing a Unifying Unit and Scale of Resistance

2018 ◽  
Author(s):  
Rudolf Fullybright
Keyword(s):  
Drug Resistance ◽  
Living Organism ◽  
Pathogen Resistance ◽  
Absolute Quantification ◽  
Biological Resistance ◽  
The Third ◽  
Exact Measurement ◽  
Unit Function ◽  
Third Law ◽  
Accurate Quantification

Accurate quantification of biological resistance has been impossible so far. Among the various forms of biological resistance which exist in nature, pathogen resistance to drugs is a familiar one. However, as in the case of other forms of resistance, accurately quantifying drug resistance in pathogens has been impossible up to now. Here, we introduce a mathematically-defined and uniform procedure for the absolute quantification of biological resistance deployed by any living organism in the biological realm, including and beyond drug resistance in medicine. The scheme introduced makes possible the exact measurement or computation of the extent to which resistance is deployed by any living organism regardless of kingdom and regardless of the mechanism of resistance involved. Furthermore, the Second Law of Resistance indicating that resistance has the potential to increase to infinite levels, and the Third Law of Resistance indicating that resistance comes to an end once interaction stops, the resistance unit function introduced here is fully compatible with both the Second and Third Laws of Resistance.

Mutant IκBα Suppresses Hypoxia-Induced VEGF Expression Through Downregulation of HIF-1α and COX-2 in Human Glioma Cells

2005 ◽  
Vol 15 (3) ◽  
pp. 139-149 ◽  
Author(s):  
Yoshihira Kimba ◽  
Tatsuya Abe ◽  
Jian Liang Wu ◽  
Ryo Inoue ◽  
Minoru Fukiki ◽  
...  
Keyword(s):  
Glioma Cells ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Vegf Expression ◽  
Cox 2

Targeting IDH Mutations in AML: Wielding the Double-edged Sword of Differentiation

2020 ◽  
Vol 20 (7) ◽  
pp. 490-500 ◽  
Author(s):  
Justin S. Becker ◽  
Amir T. Fathi
Keyword(s):  
Genome Structure ◽  
Cellular Metabolism ◽  
Standard Of Care ◽  
Competitive Inhibitor ◽  
Driver Mutations ◽  
New Class ◽  
Regulatory Enzymes ◽  
Idh Mutations ◽  
Genomic Characterization

The genomic characterization of acute myeloid leukemia (AML) by DNA sequencing has illuminated subclasses of the disease, with distinct driver mutations, that might be responsive to targeted therapies. Approximately 15-23% of AML genomes harbor mutations in one of two isoforms of isocitrate dehydrogenase (IDH1 or IDH2). These enzymes are constitutive mediators of basic cellular metabolism, but their mutated forms in cancer synthesize an abnormal metabolite, 2- hydroxyglutarate, that in turn acts as a competitive inhibitor of multiple gene regulatory enzymes. As a result, leukemic IDH mutations cause changes in genome structure and gene activity, culminating in an arrest of normal myeloid differentiation. These discoveries have motivated the development of a new class of selective small molecules with the ability to inhibit the mutant IDH enzymes while sparing normal cellular metabolism. These agents have shown promising anti-leukemic activity in animal models and early clinical trials, and are now entering Phase 3 study. This review will focus on the growing preclinical and clinical data evaluating IDH inhibitors for the treatment of IDH-mutated AML. These data suggest that inducing cellular differentiation is central to the mechanism of clinical efficacy for IDH inhibitors, while also mediating toxicity for patients who experience IDH Differentiation Syndrome. Ongoing trials are studying the efficacy of IDH inhibitors in combination with other AML therapies, both to evaluate potential synergistic combinations as well as to identify the appropriate place for IDH inhibitors within existing standard-of-care regimens.

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