scholarly journals SPME-LC/MS-based serum metabolomic phenotyping for distinguishing ovarian cancer histologic subtypes: a pilot study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mariola Olkowicz ◽  
Hernando Rosales-Solano ◽  
Vathany Kulasingam ◽  
Janusz Pawliszyn
Keyword(s):  
Ovarian Cancer ◽  
Operating Characteristic ◽  
Solid Phase ◽  
Gynecological Cancer ◽  
Serum Samples ◽  
Metabolomic Profiling ◽  
Metabolomic Data ◽  
Wide Range ◽  
Auc Value ◽  
Comprehensive Mapping

AbstractEpithelial ovarian cancer (EOC) is the most common cause of death from gynecological cancer. The outcomes of EOC are complicated, as it is often diagnosed late and comprises several heterogenous subtypes. As such, upfront treatment can be highly challenging. Although many significant advances in EOC management have been made over the past several decades, further work must be done to develop early detection tools capable of distinguishing between the various EOC subtypes. In this paper, we present a sophisticated analytical pipeline based on solid-phase microextraction (SPME) and three orthogonal LC/MS acquisition modes that facilitates the comprehensive mapping of a wide range of analytes in serum samples from patients with EOC. PLS-DA multivariate analysis of the metabolomic data was able to provide clear discrimination between all four main EOC subtypes: serous, endometrioid, clear cell, and mucinous carcinomas. The prognostic performance of discriminative metabolites and lipids was confirmed via multivariate receiver operating characteristic (ROC) analysis (AUC value > 88% with 20 features). Further pathway analysis using the top 57 dysregulated metabolic features showed distinct differences in amino acid, lipid, and steroids metabolism among the four EOC subtypes. Thus, metabolomic profiling can serve as a powerful tool for complementing histology in classifying EOC subtypes.

scholarly journals Detection of the Ovarian Cancer Biomarker Lysophosphatidic Acid in Serum

Biosensors ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 13 ◽  
Author(s):  
Brian De La Franier ◽  
Michael Thompson
Keyword(s):  
Ovarian Cancer ◽  
Lysophosphatidic Acid ◽  
Limit Of Detection ◽  
Solid Phase ◽  
Medical Condition ◽  
Large Population ◽  
Rapid Screening ◽  
Phase System ◽  
Serum Samples ◽  
Early Results

Lysophosphatidic acid (LPA) is present during the medical condition of ovarian cancer at all stages of the disease, and, therefore possesses considerable potential as a biomarker for screening its presence in female patients. Unfortunately, there is currently no clinically employable assay for this biomarker. In the present work, we introduce a test based on the duel protein system of actin and gelsolin that could allow the quantitative measurement of LPA in serum samples in a biosensing format. In order to evaluate this possibility, actin protein was dye-modified and complexed with gelsolin protein, followed by surface deposition onto silica nanoparticles. This solid-phase system was exposed to serum samples containing various concentrations of LPA and analyzed by fluorescence microscopy. Measurements conducted for the LPA-containing serum samples were higher after exposure to the developed test than samples without LPA. Early results suggest a limit of detection of 5 μM LPA in serum. The eventual goal is to employ the chemistry described here in a biosensor configuration for the large population-scale, rapid screening of women for the potential occurrence of ovarian cancer.

scholarly journals Kinetics of HE4 and CA125 as prognosis biomarkers during neoadjuvant chemotherapy in advanced epithelial ovarian cancer

2021 ◽  
Author(s):  
Jorge A. Alegría-Baños ◽  
José C. Jiménez-López ◽  
Arely Vergara-Castañeda ◽  
David F. Cantú de León ◽  
Alejandro Mohar-Betancourt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Epithelial Ovarian Cancer ◽  
Gynecological Cancer ◽  
Response To Treatment ◽  
Serum Samples ◽  
Prospective Longitudinal Study ◽  
Advanced Stages ◽  
Advanced Epithelial Ovarian Cancer ◽  
Prospective Longitudinal

Abstract Background Ovarian cancer (OC) is considered the most lethal gynecological cancer, of which more than 65% cases are diagnosed in advanced stages, requiring platinum-based neoadjuvant chemotherapy (NACT). Methods A prospective-longitudinal study was conducted among women with advanced epithelial ovarian cancer (AEOC), III and IV stages, and treated with NACT, at the National Cancer Institute – Mexico, from July 2017 to July 2018. Serum samples were obtained for quantification of CA125 and HE4 using ELISA at the first and in each of the three NACT cycles. The therapeutic response was evaluated through standard tomography. We determined whether CA125 and HE4, alone or in combination, were associated with TR to NACT during follow up. Results 53 patients aged 38 to 79 years were included, 92.4% presented papillary serous subtype OC. Higher serum HE4 levels were observed in patients with non-tomographic response (6.89 vs 5.19 pmol/mL; p = 0.031), specially during the second (p = 0.039) and third cycle of NACT (p = 0.031). Multivariate-adjusted models showed an association between HE4 levels and TR, from the second treatment cycle (p = 0.042) to the third cycle (p = 0.033). Changes from baseline HE4 levels during the first cycle was negative associated with TR. No associations were found between CA125 and TR. Conclusions Serum HE4 levels were independently associated with TR among patients with AOEC treated with NACT, also a reduction between baseline HE4 and first chemotherapy levels was also independently associated with the TR. These findings might be relevant for predicting a lack of response to treatment.

Expression Profiles of Genes Involved in Poor Prognosis of Epithelial Ovarian Carcinoma: A Review

2009 ◽  
Vol 19 (6) ◽  
pp. 992-997 ◽  
Author(s):  
Shozo Yoshida ◽  
Naoto Furukawa ◽  
Shoji Haruta ◽  
Yasuhito Tanase ◽  
Seiji Kanayama ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Gynecological Cancer ◽  
Cancer Prognosis ◽  
Specific Expression ◽  
Mesenchymal Transition ◽  
Wide Range

Background:Epithelial ovarian cancer (EOC) is the commonest cause of gynecological cancer-related mortality. Although the prognosis for patients with advanced cancer is poor, there is a wide range of outcomes for individual patients.Objective:The aim of this study was to review molecular factors predictive of poor prognosis of women with EOC by reviewing microarray research identifying gene expression profiles.Methods:A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2008, combining the keywords "genome-wide," "microarray," "epithelial ovarian cancer" "prognosis," and "epithelial-mesenchymal transition" with specific expression profiles of genes.Results:Many genes that participated in cell signaling, growth factors, transcription factors, proteinases, metabolism, cell adhesion, extracellular matrix component, cell proliferation, and anti-apoptosis were overexpressed in patients with poor prognosis. Several important prognosis-related genes overlap with those known to be regulated by epithelial-mesenchymal transition (EMT). This signaling pathway of EMT (E-cadherin, β-catenin, receptor tyrosine kinases, NF-κB, TGF-β, or Wnt signalings) will be discussed, as it provides new insights into a new treatment strategy.Conclusions:This review summarizes recent advances in prognosis-related molecular biology. Collectively, molecular changes possibly through EMT are considered to be a major contributor to the poor prognosis of EOC.

scholarly journals Per- and polyfluoroalkyl substances (PFASs) in Swedish household dust and exposure of pet cats

2021 ◽  
Author(s):  
Jana M. Weiss ◽  
Bernt Jones ◽  
Jacco Koekkoek ◽  
Anders Bignert ◽  
Marja H. Lamoree
Keyword(s):  
Thyroid Hormone ◽  
Solid Phase ◽  
Serum Levels ◽  
Mass Spectrometry Analysis ◽  
Household Dust ◽  
Serum Samples ◽  
Spectrometry Analysis ◽  
Exposure Pathway ◽  
Wide Range ◽  
Polyfluoroalkyl Substances

AbstractPer- and polyfluoroalkyl substances (PFASs) are used in a wide range of products and have been found ubiquitously in our indoor environment, and there is evidence that exposure to PFAS can lead to adverse endocrine effects, such as thyroid hormone disruption. Pet cats have a high dust intake due to their grooming behavior and have been shown to be a suitable sentinel species for assessment of toddler’s exposure. Here we used paired household dust (n=46) and cat serum (n=27) samples to establish whether dust is a relevant exposure pathway to PFASs. An analytical method for PFAS analysis was optimized using a low volume of cat serum samples, combining solid-phase extraction and online sample cleanup. Dust was extracted with methanol by sonication and cleaned up by addition of active carbon. In total, 27 PFASs were analyzed by liquid chromatography/mass spectrometry analysis. The correlation between PFAS levels in dust and serum, serum lipids and thyroid hormone levels, and PFAS levels in dust between different rooms were statistically evaluated. PFOS and PFDA could be quantified in all cat serum samples (median 2300 pg/mL and 430 pg/mL, respectively), followed by PFOA (median 1100 pg/mL), quantified in 96% of the samples. The levels of 6:2 and 8:2 diPAPs were determined in 65% and 92% of the serum samples, respectively, and were an order of magnitude lower (1.4–160 pg/mL). Household dust on the other hand was dominated by 6:2 and 8:2 diPAPs, with a median of 65 ng/g dust and 49 ng/g dust, respectively. PFOS (median 13 ng/g dust) and PFOA (median 9 ng/g dust) were quantified in 93% of the dust samples. Only eight PFASs were detected (>LOD) in at least 50% of the samples of both matrices and could be paired. Significant correlations between cat serum and dust were found for PFOA (rS=0.32, p<0.049) and PFUnDA (rS=0.55, p<0.001). Significant positive correlations were found between serum total thyroxine (rS=0.11, p<0.05) and PFNA and between serum cholesterol and PFHpA (rS=0.46, p<0.01), PFUnDA (rS=0.40, p<0.05), PFDoDA (rS=0.44, p<0.01), and sum PFAS (rS=0.48, p<0.01). In conclusion, this study confirmed that dust is a relevant exposure pathway for the ingestion of some PFASs for cats, and the serum levels of PFASs could be of relevance for the cat’s health.

scholarly journals Kinetics of HE4 and CA125 as prognosis biomarkers during neoadjuvant chemotherapy in advanced epithelial ovarian cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jorge A. Alegría-Baños ◽  
José C. Jiménez-López ◽  
Arely Vergara-Castañeda ◽  
David F. Cantú de León ◽  
Alejandro Mohar-Betancourt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Epithelial Ovarian Cancer ◽  
Gynecological Cancer ◽  
Response To Treatment ◽  
Serum Samples ◽  
Prospective Longitudinal Study ◽  
Advanced Stages ◽  
Advanced Epithelial Ovarian Cancer ◽  
Prospective Longitudinal

Abstract Background Ovarian cancer (OC) is considered the most lethal gynecological cancer, of which more than 65% cases are diagnosed in advanced stages, requiring platinum-based neoadjuvant chemotherapy (NACT). Methods A prospective-longitudinal study was conducted among women with advanced epithelial ovarian cancer (AEOC), III and IV stages, and treated with NACT, at the National Cancer Institute – Mexico, from July 2017 to July 2018. Serum samples were obtained for quantification of CA125 and HE4 using ELISA at the first and in each of the three NACT cycles. The therapeutic response was evaluated through standard tomography. We determined whether CA125 and HE4, alone or in combination, were associated with TR to NACT during follow up. Results 53 patients aged 38 to 79 years were included, 92.4% presented papillary serous subtype OC. Higher serum HE4 levels were observed in patients with non-tomographic response (6.89 vs 5.19 pmol/mL; p = 0.031), specially during the second (p = 0.039) and third cycle of NACT (p = 0.031). Multivariate-adjusted models showed an association between HE4 levels and TR, from the second treatment cycle (p = 0.042) to the third cycle (p = 0.033). Changes from baseline HE4 levels during the first cycle was negative associated with TR. No associations were found between CA125 and TR. Conclusions Serum HE4 levels were independently associated with TR among patients with AOEC treated with NACT, also a reduction between baseline HE4 and first chemotherapy levels was also independently associated with the TR. These findings might be relevant for predicting a lack of response to treatment.

Multicenter evaluation of human placental alkaline phosphatase as a possible tumor-associated antigen in serum.

1988 ◽  
Vol 34 (10) ◽  
pp. 1995-1999 ◽  
Author(s):  
M E De Broe ◽  
D E Pollet
Keyword(s):  
Ovarian Cancer ◽  
Alkaline Phosphatase ◽  
Testicular Cancer ◽  
Cancer Patients ◽  
Solid Phase ◽  
Ca 125 ◽  
Placental Alkaline Phosphatase ◽  
Serum Samples ◽  
Heavy Smoking ◽  
Human Placental Alkaline Phosphatase

Abstract Using a solid-phase monoclonal antibody enzyme immuno-assay, we evaluated in a multicenter study (18 laboratories) the utility of evaluating catalytic activity of human placental alkaline phosphatase (hPLAP, EC 3.1.3.1) in serum as a potential tumor marker. We determined hPLAP in serum samples from 130 patients with ovarian cancer, 79 patients with testicular cancer (53 seminoma testis, 26 nonseminoma testis), 537 patients with various other malignant diseases (95 lung, 39 gastrointestinal, 195 breast, 208 others), 291 patients with benign diseases, and 213 healthy controls. To assess the influence of smoking on hPLAP activity in serum, we evaluated 79 serum samples from patients with noncancerous diseases for whom smoking habits had been recorded. Our main findings are: (a) hPLAP activity is frequently increased (greater than 100 mU/L) in pre-operative serum samples from ovarian cancer patients (49%) and from testicular cancer patients (59% overall; 72% seminoma, 35% nonseminoma); (b) heavy smoking may increase hPLAP activity; (c) excluding heavy smokers, a 96% specificity for cancerous lesions was observed; (d) in patients with ovarian malignancies, CA 125 and hPLAP may behave as independent markers; and (e) in patients with seminoma, hPLAP is clearly more frequently increased than is beta-choriogonadotropin.

scholarly journals Serum Metabolomic Profiling of Patients with Non-Infectious Uveitis

2020 ◽  
Vol 9 (12) ◽  
pp. 3955
Author(s):  
Hiroyuki Shimizu ◽  
Yoshihiko Usui ◽  
Masaki Asakage ◽  
Naoya Nezu ◽  
Ryo Wakita ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Operating Characteristic ◽  
The Other ◽  
Serum Samples ◽  
Logistic Regression Models ◽  
Minimal Invasiveness ◽  
Flight Mass Spectrometry ◽  
Metabolomic Profiling ◽  
Healthy Control ◽  
Infectious Uveitis

The activities of various metabolic pathways can influence the pathogeneses of autoimmune diseases, and intrinsic metabolites can potentially be used to diagnose diseases. However, the metabolomic analysis of patients with uveitis has not yet been conducted. Here, we profiled the serum metabolomes of patients with three major forms of uveitis (Behҫet’s disease (BD), sarcoidosis, and Vogt-Koyanagi-Harada disease (VKH)) to identify potential biomarkers. This study included 19 BD, 20 sarcoidosis, and 15 VKH patients alongside 16 healthy control subjects. The metabolite concentrations in their sera were quantified using liquid chromatography with time-of-flight mass spectrometry. The discriminative abilities of quantified metabolites were evaluated by four comparisons: control vs. three diseases, and each disease vs. the other two diseases (such as sarcoidosis vs. BD + VKH). Among 78 quantified metabolites, 24 kinds of metabolites showed significant differences in these comparisons. Four multiple logistic regression models were developed and validated. The area under the receiver operating characteristic (ROC) curve (AUC) in the model to discriminate disease groups from control was 0.72. The AUC of the other models to discriminate sarcoidosis, BD, and VKH from the other two diseases were 0.84, 0.83, and 0.73, respectively. This study provides potential diagnostic abilities of sarcoidosis, BD, and VKH using routinely available serum samples that can be collected with minimal invasiveness.

Analysis of Aromatic Amines in Industrial Wastewater by Capillary Gas Chromatography-Mass Spectrometry

2000 ◽  
Vol 35 (2) ◽  
pp. 245-262 ◽  
Author(s):  
Francis I. Onuska ◽  
Ken A. Terry ◽  
R. James Maguire
Keyword(s):  
Gas Chromatography ◽  
Aromatic Amines ◽  
Methylene Chloride ◽  
Solid Phase ◽  
Stationary Phases ◽  
Gas Chromatography Mass Spectrometry ◽  
Substituted Anilines ◽  
Environmental Media ◽  
Solid Phase Extraction Cartridge ◽  
Wide Range

Abstract The analysis of aromatic amines, particularly benzidines, at trace levels in environmental media has been difficult because of the lack of suitable deactivated capillary column stationary phases for gas chromatography. This report describes the use of an improved type of column as well as a method for the analysis of anilines and benzidines in water, wastewater and sewage samples. Extraction procedures are applicable to a wide range of compounds that are effectively partitioned from an aqueous matrix into methylene chloride, or onto a solid-phase extraction cartridge. The extracted analytes are also amenable to separation on a capillary gas chromatographic column and transferable to the mass spectrometer. These contaminants are converted to their N-trifluoroacetyl derivatives. Aniline and some substituted anilines, and 3,3’-dichlorobenzidine and benzidine were determined in 24-h composite industrial water, wastewater, primary sludge and final effluent samples at concentrations from 0.03 up to 2760 µg/L.

Recent Application of Polystyrene-supported Triphenylphosphine in Solid-Phase Organic Synthesis

2019 ◽  
Vol 23 (6) ◽  
pp. 643-678
Author(s):  
Lalthazuala Rokhum ◽  
Ghanashyam Bez
Keyword(s):  
Organic Synthesis ◽  
Combinatorial Chemistry ◽  
Solid Phase ◽  
Recent Application ◽  
Organic Transformations ◽  
Solid Phase Organic Synthesis ◽  
Wide Range ◽  
Fast Development ◽  
Polymer Supported

Recent years have witnessed a fast development of solid phase synthetic pathways, a variety of solid-supported reagent and its applications in diverse synthetic strategies and pharmaceutical applicability’s. Polymer-supported triphenylphosphine is getting a lot of applications owing to the speed and simplicity in the process. Furthermore, ease of recyclability and reuse of polymer-supported triphenylphosphine added its advantages. This review covers a wide range of useful organic transformations which are accomplished using cross-linked polystyrene-supported triphenylphosphine with the aim of giving renewed interest in the field of organic and medicinal-combinatorial chemistry.

scholarly journals UHPLC-ESI-MS/MS Quantification of Relevant Substrates and Metabolites of the Kynurenine Pathway Present in Serum and Peritoneal Fluid from Gastric Cancer Patients—Method Development and Validation

2021 ◽  
Vol 22 (13) ◽  
pp. 6972
Author(s):  
Ilona Sadok ◽  
Katarzyna Jędruchniewicz ◽  
Karol Rawicz-Pruszyński ◽  
Magdalena Staniszewska
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Peritoneal Fluid ◽  
Method Development ◽  
Solid Phase ◽  
Kynurenine Pathway ◽  
Serum Samples ◽  
Esi Ms ◽  
Gastric Cancer Patients ◽  
Development And Validation

Metabolites and enzymes involved in the kynurenine pathway (KP) are highly promising targets for cancer treatment, including gastrointestinal tract diseases. Thus, accurate quantification of these compounds in body fluids becomes increasingly important. The aim of this study was the development and validation of the UHPLC-ESI-MS/MS methods for targeted quantification of biologically important KP substrates (tryptophan and nicotinamide) and metabolites(kynurenines) in samples of serum and peritoneal fluid from gastric cancer patients. The serum samples were simply pretreated with trichloroacetic acid to precipitate proteins. The peritoneal fluid was purified by solid-phase extraction before analysis. Validation was carried out for both matrices independently. Analysis of the samples from gastric cancer patients showed different accumulations of tryptophan and its metabolites in different biofluids of the same patient. The protocols will be used for the evaluation of tryptophan and kynurenines in blood and peritoneal fluid to determine correlation with the clinicopathological status of gastric cancer or the disease’s prognosis.

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