Utility of Kinetic, Dynamic, and Metabolic Data in Nonclinical Pharmacology/Toxicology Studies

Author(s):  
Judi Weissinger
Keyword(s):  
1993 ◽  
Vol 8 (S3) ◽  
pp. S128-S129
Author(s):  
C.S De Deyne ◽  
J.M Decruyenaere ◽  
J.I Poelaert ◽  
F.A Colardyn

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi13-vi13
Author(s):  
Noriaki Minami ◽  
Donghyun Hong ◽  
Nicholas Stevers ◽  
Georgios Batsios ◽  
Anne Marie Gillespie ◽  
...  

Abstract BACKGROUND TERT promoter mutations that result in TERT expression are observed in over 80% of GBM. Moreover, the upstream transcription factor GABPB1 was recently identified as an ideal therapeutic target for tumors with TERT promoter mutations. In that context, non-invasive reliable biomarkers that can help detect TERT expression are needed. The aim of this research was to assess the value of MRS-detectable metabolic changes as biomarkers of TERT expression and TERT-targeted therapy in GBM. METHODS Genetically engineered GBM cells (NHARas/TERT) treated with TERT siRNA were compared to siCtrl-treated cells, and stable TERT and GABPB1 knock down GBM cells (U251, GBM1) were compared to shCtrl. 1H-MRS and 13C-MRS metabolic data was acquired from cell extracts using a Bruker 500MHz scanner. Hyperpolarized MRS studies of live cells used a HyperSense DNP polarizer and data was acquired using a Varian 500MHz scanner. Spectra were analyzed using Mnova and Matlab software. Multivariate data analysis was performed using SIMCA software. RESULTS Unbiased PCA analysis of 1H-MRS metabolic data showed separation of TERT or GABPB1 knock down and control cells. VIP predictive scores revealed that lactate and GSH were the top altered metabolites with a significant drop observed in both metabolites in every model following TERT silencing. Consistent with the reduction in GSH, spectrophotometric assays showed a significant drop in NADPH and NADH. 2-13C glucose flux analysis revealed that both glycolysis and PPP-related metabolites were reduced in TERT knock down cells. Hyperpolarized [1-13C]-pyruvate flux to lactate was also reduced, confirming that the glycolytic pathway was altered following TERT knock down. CONCLUSION 1H MRS-detectable lactate and GSH, combined with hyperpolarized 13C MRS-detectable metabolic fluxes, could serve as metabolic biomarkers of TERT-targeted therapy for human GBM with TERT promoter mutations. These biomarkers could be translated to the clinical, improve the monitoring of GBM patients and advance precision medicine.


PEDIATRICS ◽  
1977 ◽  
Vol 60 (4) ◽  
pp. 633-637
Author(s):  
Harry H. Gordon

When John Bartram phoned to tell me of this greatly appreciated honor, he said I could speak to whatever topic I chose. Implicit in such trust was the assumption that I would be brief. Dr. Aldrich played a major role in bringing the practice of infant feeding from an era of pseudo-scientific misapplication of metabolic data into a psychologic era.1 He recognized that feeding was the the most important early transaction between mother and infant and that appropriate pediatric advice could promote healthy personality development. His wisdom was derived from a large experience with mothers and babies, and a grounding in the philosophic concepts of Ralph Waldo Emerson: "Respect the child. Be not too much his parent. . . . Respect the child, respect him to the end, but also respect yourself."2 I propose to address briefly the lack of respect by some pediatricians for the felt needs of mothers. Dr. Aldrich saw the mother and infant as a unit. He considered the term "self-demand" feeding too autocratic and substituted "self-regulation," recognizing that limits should be set which respected the mother and her other responsibilities as well as the infant. He preferred a schedule of feeding which was neither rigid, leading to anorexia, nor virtually nonexistent, leading to early obesity and what Spock termed chronic resistance to sleep, the latter a family affair with tensions for father as well as mother. His conceptualization led us to summarize our own laboratory observations under the title, "A Metabolic Basis for the Individualized Feeding of Young Infants," and to a later study of self-regulation of intake of food by prematurely born infants, a step toward flexible, sound advice to anxious mothers on discharge of their infants.3


2018 ◽  
pp. 177-192
Author(s):  
John R. B. Lighton

This chapter discusses ways of analyzing and presenting metabolic data while avoiding common mistakes. Topics covered include vital information often omitted from manuscripts; how to analyze the allometry of metabolic rate on mass; the mistake of reporting mass-specific or “mass-independent” metabolic rates; methods for quantifying differences between treatment groups by analysis of covariance; the importance of phylogeny in interspecific comparisons; the importance of the temperature at which measurements are made, including mammals (the thermal neutral zone); the necessity of leaving an “audit trail” from raw data through to final analysis; analyzing temperature effects such as Q10 correctly; and the proper selection of metabolic data.


Sign in / Sign up

Export Citation Format

Share Document