The tumor microenvironment (TME) comprises a heterogeneous number and type of cellular and noncellular components that vary in the context of molecular, genomic and epigenomic levels. The genotypic diversity and plasticity within cancer cells are known to be affected by genomic instability and genome alterations. Besides genomic instability within the chromosomal linear DNA, an extra factor appears in the form of extrachromosomal circular DNAs (eccDNAs; 2–20 kbp) and microDNAs (200–400 bp). This extra heterogeneity within cancer cells in the form of an abundance of eccDNAs adds another dimension to the expression of procancer players, such as oncoproteins, acting as a driver for cancer cell survival and proliferation. This article reviews research into eccDNAs centering around cancer plasticity and hallmarks, and discusses these facts in light of therapeutics and biomarker development.

1. G.l.c.--mass spectral analysis of t.l.c. fractions of urine samples of patients treated with 5-(2-chloroethyl)-4-methylthiazole (clomethiazole), has revealed two minor metabolites, each with two sulphur atoms. 2. Their structures were found to be 2-methylthio-clomethiazole and 5-acetyl-4-methyl-2-mercapto-thiazole, formed by thiomethylation and thiohydroxylation, respectively, of the original compound. 3. The structures of six other minor metabolites resulting from side-chain degradation have been elucidated. 4. The occurrence of metabolites with substituents at position 2 of the heterocyclic nucleus is assumed to be initiated by oxidative attack at the nitrogen, followed by nucleophilic substitution in position 2.

Background:In recent, various human health disorders including cancer, diabetes, neurodegenerative and metabolic diseases are noticed among human populations. Currently, genetic and proteomic approaches are highly reported to detect metabolic disorders that also include inborn error of metabolisms. These existing detection methods are faced with cost issue and time consuming factors. Therefore, metabolites as biomarkers are one of potential avenues to detect metabolic disorders. Further, exploitation of urine as potential source of metabolite biomarkers, there are limitation in this area of research due to abundance of non-metabolite components such as proteins and nucleic acids. Hence, methods and processes are required to precisely fractionate metabolites from urine of inborn error of metabolism patients and then identified by analytical tools such as LC-HRMS and GC-MS.Methods: Sterile filtered urine samples (750 µl) mixed with (250 µl) loading buffer were electrophoresed on VTGE that uses acrylamide gel (acrylamide:bisacrylamide, 30:1) as matrix of 15%. Further, vertical tube gel electrophoresis (VTGE) technique combined with LC-HR-MS to identify metabolites that are known as the biomarkers of metabolic disorders was carried out. Results and Discussion:The authors provide evidence on the use of novel VTGE coupled with LC-HRMS to detect metabolites among metabolic disorders. Data suggest the applicability of VTGE coupled with LC-HRMS technique to detect metabolites such as 2-methyluridine, 2-Methylglutaric acid, 2-Methyl citric acid, 2-Hydroxyglutaric acid in case of metabolic disorders. Conclusion:This preliminary work is suggested to be extended to large clinical samples to validate application of this method to detect metabolic disorders including inborn error of metabolisms.