scholarly journals Integrative Metabolomic and Transcriptomic Analysis for the Study of Bladder Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 686 ◽  
Author(s):  
Alba Loras ◽  
Cristian Suárez-Cabrera ◽  
M. Carmen Martínez-Bisbal ◽  
Guillermo Quintás ◽  
Jesús M. Paramio ◽  
...  
Keyword(s):  
Amino Acids ◽  
Bladder Cancer ◽  
Tricarboxylic Acid Cycle ◽  
Tumor Biology ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
Tissue Samples ◽  
Invasive Approach ◽  
Non Invasive ◽  
Angle Spinning

Metabolism reprogramming is considered a hallmark of cancer. The study of bladder cancer (BC) metabolism could be the key to developing new strategies for diagnosis and therapy. This work aimed to identify tissue and urinary metabolic signatures as biomarkers of BC and get further insight into BC tumor biology through the study of gene-metabolite networks and the integration of metabolomics and transcriptomics data. BC and control tissue samples (n = 44) from the same patients were analyzed by High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance and microarrays techniques. Besides, urinary profiling study (n = 35) was performed in the same patients to identify a metabolomic profile, linked with BC tissue hallmarks, as a potential non-invasive approach for BC diagnosis. The metabolic profile allowed for the classification of BC tissue samples with a sensitivity and specificity of 100%. The most discriminant metabolites for BC tissue samples reflected alterations in amino acids, glutathione, and taurine metabolic pathways. Transcriptomic data supported metabolomic results and revealed a predominant downregulation of metabolic genes belonging to phosphorylative oxidation, tricarboxylic acid cycle, and amino acid metabolism. The urinary profiling study showed a relation with taurine and other amino acids perturbed pathways observed in BC tissue samples, and classified BC from non-tumor urine samples with good sensitivities (91%) and specificities (77%). This urinary profile could be used as a non-invasive tool for BC diagnosis and follow-up.

Solid-state NMR approaches to investigate large enzymes in complex with substrates and inhibitors

2020 ◽  
Author(s):  
Anne K. Schütz
Keyword(s):  
Solid State ◽  
Solid State Nmr ◽  
Magic Angle Spinning ◽  
Enzyme Mechanism ◽  
Invasive Technique ◽  
Magic Angle ◽  
Specific Chemical ◽  
Non Invasive ◽  
Multiple Assets ◽  
Angle Spinning

Enzyme catalysis is omnipresent in the cell. The mechanisms by which highly evolved protein folds enable rapid and specific chemical transformation of substrates belong to the marvels of structural biology. Targeting of enzymes with inhibitors has immediate application in drug discovery, from chemotherapeutics over antibiotics to antivirals. NMR spectroscopy combines multiple assets for the investigation of enzyme function. The non-invasive technique can probe enzyme structure and dynamics and map interactions with substrates, cofactors and inhibitors at the atomic level. With experiments performed at close to native conditions, catalytic transformations can be monitored in real time, giving access to kinetic parameters. The power of NMR in the solid state, in contrast with solution, lies in the absence of fundamental size limitations, which is crucial for enzymes that are either membrane-embedded or assemble into large soluble complexes exceeding hundreds of kilodaltons in molecular weight. Here we review recent progress in solid-state NMR methodology, which has taken big leaps in the past years due to steady improvements in hardware design, notably magic angle spinning, and connect it to parallel biochemical advances that enable isotope labelling of increasingly complex enzymes. We first discuss general concepts and requirements of the method and then highlight the state-of-the-art in sample preparation, structure determination, dynamics and interaction studies. We focus on examples where solid-state NMR has been instrumental in elucidating enzyme mechanism, alone or in integrative studies.

Evaluation of31P high-resolution magic angle spinning of intact tissue samples

2006 ◽  
Vol 19 (5) ◽  
pp. 593-598 ◽  
Author(s):  
G. S. Payne ◽  
H. Troy ◽  
S. J. Vaidya ◽  
J. R. Griffiths ◽  
M. O. Leach ◽  
...  
Keyword(s):  
High Resolution ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
Tissue Samples ◽  
Intact Tissue ◽  
Angle Spinning

Magic angle spinning magnetic resonance: a novel method opening up translational research into NAFLD?

2009 ◽  
Vol 116 (5) ◽  
pp. 401-402 ◽  
Author(s):  
Chris Boesch
Keyword(s):  
Magnetic Resonance ◽  
Translational Research ◽  
Fatty Infiltration ◽  
Magic Angle Spinning ◽  
Resonance Spectroscopy ◽  
Magic Angle ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Angle Spinning ◽  
Excised Tissue

NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steatohepatitis) are of increasing importance, both in connection with insulin resistance and with the development of liver cirrhosis. Histological samples are still the ‘gold standard’ for diagnosis; however, because of the risks of a liver biopsy, non-invasive methods are needed. MAS (magic angle spinning) is a special type of NMR which allows characterization of intact excised tissue without need for additional extraction steps. Because clinical MRI (magnetic resonance imaging) and MRS (magnetic resonance spectroscopy) are based on the same physical principle as NMR, translational research is feasible from excised tissue to non-invasive examinations in humans. In the present issue of Clinical Science, Cobbold and co-workers report a study in three animal strains suffering from different degrees of NAFLD showing that MAS results are able to distinguish controls, fatty infiltration and steatohepatitis in cohorts. In vivo MRS methods in humans are not obtainable at the same spectral resolution; however, know-how from MAS studies may help to identify characteristic changes in crowded regions of the magnetic resonance spectrum.

scholarly journals Metabolomics of Small Intestine Neuroendocrine Tumors and Related Hepatic Metastases

Metabolites ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 300
Author(s):  
Alessio Imperiale ◽  
Gilles Poncet ◽  
Pietro Addeo ◽  
Elisa Ruhland ◽  
Colette Roche ◽  
...  
Keyword(s):  
Small Intestine ◽  
Neuroendocrine Tumors ◽  
Hepatic Metastases ◽  
Magic Angle Spinning ◽  
Tumor Evolution ◽  
Magic Angle ◽  
Tissue Samples ◽  
Hrmas Nmr ◽  
Angle Spinning ◽  
First Time

To assess the metabolomic fingerprint of small intestine neuroendocrine tumors (SI-NETs) and related hepatic metastases, and to investigate the influence of the hepatic environment on SI-NETs metabolome. Ninety-four tissue samples, including 46 SI-NETs, 18 hepatic NET metastases and 30 normal SI and liver samples, were analyzed using 1H-magic angle spinning (HRMAS) NMR nuclear magnetic resonance (NMR) spectroscopy. Twenty-seven metabolites were identified and quantified. Differences between primary NETs vs. normal SI and primary NETs vs. hepatic metastases, were assessed. Network analysis was performed according to several clinical and pathological features. Succinate, glutathion, taurine, myoinositol and glycerophosphocholine characterized NETs. Normal SI specimens showed higher levels of alanine, creatine, ethanolamine and aspartate. PLS-DA revealed a continuum-like distribution among normal SI, G1-SI-NETs and G2-SI-NETs. The G2-SI-NET distribution was closer and clearly separated from normal SI tissue. Lower concentration of glucose, serine and glycine, and increased levels of choline-containing compounds, taurine, lactate and alanine, were found in SI-NETs with more aggressive tumors. Higher abundance of acetate, succinate, choline, phosphocholine, taurine, lactate and aspartate discriminated liver metastases from normal hepatic parenchyma. Higher levels of alanine, ethanolamine, glycerophosphocholine and glucose was found in hepatic metastases than in primary SI-NETs. The present work gives for the first time a snapshot of the metabolomic characteristics of SI-NETs, suggesting the existence of complex metabolic reality, maybe characteristic of different tumor evolution.

scholarly journals Mo1232 Employing High-Resolution Magic Angle Spinning (HR-MAS) MRS As Non-Invasive Diagnostic Approach in Non-Alcoholic Steatohepatitis (NASH)

2013 ◽  
Vol 144 (5) ◽  
pp. S-612-S-613
Author(s):  
Brittany Lee-McMullen ◽  
Keisaku Sato ◽  
Tracie Chui Lo ◽  
Huadong Zeng ◽  
Pavesh Sharma ◽  
...  
Keyword(s):  
High Resolution ◽  
Magic Angle Spinning ◽  
Diagnostic Approach ◽  
Magic Angle ◽  
Non Invasive ◽  
Alcoholic Steatohepatitis ◽  
Hr Mas Mrs ◽  
Angle Spinning

A solid-state 14N magic-angle spinning NMR study of some amino acids

2004 ◽  
Vol 166 (2) ◽  
pp. 262-272 ◽  
Author(s):  
Tania Giavani ◽  
Henrik Bildsøe ◽  
Jørgen Skibsted ◽  
Hans J Jakobsen
Keyword(s):  
Amino Acids ◽  
Solid State ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
Nmr Study ◽  
Angle Spinning
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