Current Issue : October - December Volume : 2020 Issue Number : 4 Articles : 5 Articles
Introduction: The activity of butyrylcholinesterase (BChE) in blood reflects liver function\nand has recently been associated with systemic inflammatory response and tumor cachexia. As these\nconditions have been previously linked with pancreatic cancer (PC), the purpose of the present study\nwas to evaluate the prognostic impact of plasma BChE in PC. Methods: Data from 574 consecutive\nPC patients, treated between 2004 and 2018 at a single academic center, was evaluated. The primary\nendpoint was cancer-specific survival (CSS), analyzed by Kaplanâ??Meier curve, and both univariate\nand multivariate Cox proportional models. Results: BChE activity negatively correlated with other\nliver parameters (bilirubin, gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST),\nalkaline phosphatase (ALP), and C-reactive protein (CRP)), and positively correlated with albumin\nlevels, respectively (p < 0.01). In univariate analysis, a low plasma BChE activity was a factor of\npoor CSS (hazard ratio: 1.4, 95% confidence interval: 1.129â??1.754, p = 0.002). In multivariate analysis,\ntumor stage, tumor grade, administration of chemotherapy, bilirubin levels and a low BChE activity\n(hazard ratio: 1.42, 95% confidence interval: 1.10â??1.82; p = 0.006) were identified as independent\nprognostic factors. Conclusion: Decreased activity of BChE in blood plasma predicts shorter survival\ntime in PC patients. Therefore, BChE might be helpful in additional stratification of patients into\ndierent prognostic risk groups....
Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasiaâ??the early recognition of which may allow fertility sparing management and cancer prevention....
Silybin is a flavonolignan extracted from Silybum marianum with chemopreventive activity\nagainst various cancers, including breast. This study was designed to develop an HPLC-MS/MS\nmethod for the determination of silybin in human plasma, urine and breast tissue in early breast\ncancer patients undergoing Siliphos® supplementation, an oral silybin-phosphatidylcholine complex.\nThe determination of silybin was carried out by liquidâ??liquid extraction with methyl-tert-butyl ether\n(MTBE); total silybin concentration was determined by treating the samples with Betaâ??glucuronidase,\nwhile for the determination of free silybin, the hydrolytic step was omitted. Naringenin and naproxen\nwere selected as internal standards. The detection of the analyte was carried out by mass spectrometry\nand by chromatography. The HPLC-MS/MS method was evaluated in terms of selectivity, linearity,\nlimit of quantification, precision and accuracy, and carryover. The method proved to be selective,\nlinear, precise and accurate for the determination of silybin. To the best of our knowledge, this presents\nthe first analytical method with the capacity to quantify the major bioactive components of milk\nthistle in three different biological matrices with a lower limit of quantification of 0.5 ng/mL for\nplasma. Silybin phosphatidylcholine, taken orally, can deliver high blood concentrations of silybin,\nwhich selectively accumulates in breast tumor tissue....
A magnetic solid phase extraction technique followed by liquid chromatography with a\nfluorescence detector for naproxen analysis in human urine samples was developed. The method\nincludes the extraction of naproxen with a magnetic solid synthetized with magnetite and poly\n4-vinylpriridine, followed by the magnetic separation of the solid phase and desorption of the analyte\nwith methanol. Under optimal conditions, the linear range of the calibration curve was 0.05â??0.60 microg\nL-1, with a limit of detection of 0.02 microg L-1. In all cases values of repeatability were lower than\n5.0% with recoveries of 99.4 1.3%. Precision and accuracy values are adequate for naproxen (Npx)\nanalysis in urine samples....
The third-generation tyrosine kinase inhibitor (TKI), osimertinib, has revolutionized the\ntreatment of patients with non-small cell lung carcinoma with epidermal growth factor receptor\n(EGFR)-activating mutation, and resistant to first- and second-generation TKIs. Osimertinib isnow also\nproposed as a first-line therapy, thus extending the scope of applications in lung oncology. Personalized\nmedicine approaches are still necessary to monitor if patients are exposed to adequate concentrations of\nosimertinib during their treatment. It would also help to understand the appearance of new resistances\nin patients after several months of dosing with osimertinib. Liquid chromatographyâ??tandem mass\nspectrometry (LCâ??MS/MS) is currently the gold standard for the quantification of drugs in plasma\nenabling pharmacokinetic analyses and patient monitoring. In the present study, we propose an\nalternative to LCâ??MS/MS methods for the rapid and sensitive quantification of osimertinib in plasma\nusing matrix-assisted laser desorption/ionization (MALDI) â??MS. The presented assay requires only\n3 min per sample for their preparation, analysis, and data extraction, and less than 3 h for quantification.\nA lower limit of quantification (LLOQ) of 5 ng/mL in plasma was retrieved. The method was fully\nvalidated, following the guidelines of the US Food and Drug Administration (FDA) and the European\nMedicines Agency (EMA) for bioanalytical method validation. The present developments prove\nthe importance to consider alternative MS assays for time-effcient quantification of small molecule\ninhibitors in plasma in the context of personalized medicine for targeted therapies....
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