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Liquid Biopsies for Pancreatic Cancer: A Step Towards Early Detection
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Joseph Carmicheal, Rahat Jahan, Koelina Ganguly, Ashu Shah, Sukhwinder Kaur
Metabolomics can be defined as a robust approach to globally quantitate the measurable pool of small molecular weight intermediates of biochemical pathways, i.e. metabolites at the cell, tissue or organismal level. It exists at the bottom of the “omics” cascade and closely reflects variations in the phenotypic state of a biological system resulting from endogenous and/or exogenous influences [29]. Considering the dynamicity of living systems, genomics, transcriptomics, and proteomics often fail to mirror the actual clinical phenotype resulting from genetic/epigenetic mutations or adequately represent the specifically altered functionality of post-translationally modified enzymes. Metabolic fluxes in an organism can stem from either inherited genetic aberrations or subtle mutations in the genome. These fluxes can also result from machinery modifications acquired by the system over time due to environmental factors, gut microflora, antigen exposure, diseased state, and therapeutic interventions. Metabolomics is an emerging field of investigation with burgeoning interest amongst cancer researchers. Cancer pathogenesis is associated with hereditary predispositions, somatic mutations, and environmental exposures. Thus, combining a metabolic profile with mutational analysis may more comprehensively manifest the pathological grade, prognostic state or therapeutic response of pancreatic cancer and other malignancies.
Hereditary and Metabolic Diseases of the Central Nervous System in Adults
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Acute encephalopathy in neurometabolic disorders variously results from liver failure, hypoglycemia, or direct neurotoxic effects of ammonia (urea cycle disorders), organic acids (organic acidemias), or metal accumulation (Wilson's disease [WD]). In many small molecule intoxication-type disorders, acute symptoms can be triggered by external physiological stressors such as illness, childbirth, surgery, prolonged fasting, high protein intake, or steroid medications. These triggers induce catabolism (breakdown of proteins and other macromolecules), which overwhelms the affected biochemical pathway and leads to the accumulation of metabolic intermediates. Symptoms appear once toxic compounds accumulate to sufficient levels, which may be days or even a week after the insult. For example, encephalopathy after surgery has been reported as the first symptom of disease in many adults with late-onset/partial ornithine transcarbamylase (OTC) deficiency. In this urea cycle disorder, ammonia produced from the breakdown of amino acids is not adequately detoxified to urea, so patients develop hyperammonemic encephalopathy progressing to cerebral edema or strokes. The disease spectrum of OTC deficiency in adults includes individuals whose first ever symptom is fatal postsurgical cerebral edema after age 50 and individuals with recurrent episodes of headache, irritability, and seizure who turn out to have had recurrent hyperammonemia with cortical and subcortical infarcts.4,5
Biology of Acinetobacter spp.
Published in E. Bergogne-Bénézin, M.L. Joly-Guillou, K.J. Towner, Acinetobacter, 2020
The ability of acinetobacters to metabolise a wide range of aromatic, alicyclic and other compounds has resulted in a number of possible commercial biotransformation processes, including the production of L(-)-carnitine (see Section 2.6.1). Biotransformation processes can be achieved with either whole cells or purified enzymes, although a disadvantage implicit in the use of whole cells is the potentially rapid consecutive degradation of the products of interest. Many of the unusual biochemical pathways utilised by Acinetobacter spp. are still in the process of being elucidated, but it is already clear that it may be possible to accumulate intermediate products of commercial interest by constructing mutant strains that are blocked at the appropriate point of a particular biochemical pathway. In this respect, compared with other microorganisms of similar metabolic activity, acinetobacters have an important advantage in that they are easy to isolate, cultivate and manipulate genetically in the laboratory.
Glucose metabolism inhibitor PFK-015 combined with immune checkpoint inhibitor is an effective treatment regimen in cancer
Published in OncoImmunology, 2022
Jia Bo Zheng, Chau Wei Wong, Jia Liu, Xiao-Jing Luo, Wei-Yi Zhou, Yan-Xing Chen, Hui-Yan Luo, Zhao-Lei Zeng, Chao Ren, Xiao-Ming Xie, De-Shen Wang
Glycolysis is an essential enzymatic process in human cell metabolism. It participates in the production of substrates required in multiple biochemical pathways, such as the tricarboxylic acid cycle, pentose phosphate pathway, and fatty acids and cholesterol synthesis. In normal human cells, anaerobic reactions predominate in the metabolism under reduced oxygen conditions; however, in 1972, Otto Warburg reported an essential role of glycolysis in cancer cells regardless of oxygen concentration in the tumor microenvironment1. This reprogramming of cancer cell metabolism is not only responsible for the aggressiveness of cancer growth but may also decrease reactive oxygen species production and accumulation, and increase the abundance of key metabolites required for rapid cell growth and proliferation.2,3
Cutting-edge strategies and critical advancements in characterization and quantification of metabolites concerning translational metabolomics
Published in Drug Metabolism Reviews, 2022
Megha Sajakumar Pillai, Sree Teja Paritala, Ravi P. Shah, Nitish Sharma, Pinaki Sengupta
Altered metabolites in biofluids indicate variations in pathophysiology which can be assessed quantitatively and qualitatively as the metabolite represents the end point of the closest cascade phenotype (Yuan et al. 2012). Metabolite analysis helps to understand the alteration of diagnostic markers and examine any unknown pathophysiology by establishing a relation between phenotype and metabolite profile. This can be a potent approach in elucidating biochemical pathways for better diagnosis and treatment. Various conventional analytical tools available for quantification and identification of metabolites include nuclear magnetic resonance spectroscopy (NMR), mass technologies like gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and capillary electrophoresis-mass spectrometry (CE-MS) (Sengupta et al. 2017; Ala-Korpela 2018; Biswas et al. 2018).
Metabolic pathways and metabolites shaping innate immunity
Published in International Reviews of Immunology, 2020
Synthesis and breakdown of biomolecules through biochemical pathways in the cells for various cellular processes such as cell survival, growth, replication and so on are known as cellular metabolism. The cellular metabolism is not only essential for organization of cellular processes, but it is crucial for tailoring and shaping the host immunity to defend infection and maintain immune homeostasis. Additionally, at cellular and molecular levels, several metabolic intermediates are key deciding factors for many immunological events and induction of cytokines and hence are required to develop appropriate protective responses. Therefore, dysregulation of metabolic pathways may change the susceptibility to disease. This issue of International Reviews of Immunology describes how immunometabolism influences immunological responses, particularly, the macrophage function during vaccination. The issue also provides the possibilities of fine tuning the metabolic pathways or metabolic intermediates to treat different medical conditions (Figure-1).