Comparison between Plasma and Serum Osteopontin Levels: Usefulness in Diagnosis of Epithelial Malignant Pleural Mesothelioma

2010 ◽  
Vol 25 (3) ◽  
pp. 164-170 ◽  
Author(s):  
Alfonso Cristaudo ◽  
Rudy Foddis ◽  
Alessandra Bonotti ◽  
Silvia Simonini ◽  
Agnese Vivaldi ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Healthy Subjects ◽  
Asbestos Exposure ◽  
Control Group ◽  
Pleural Mesothelioma ◽  
Serum Samples ◽  
Temperature Plasma ◽  
Commercial Laboratory ◽  
Different Temperatures

Background A potential role of serum osteopontin (OPN) and serum mesothelin-related peptide (SMRP) in the diagnosis of malignant pleural mesothelioma (MPM) has been recently reported. Although the most important data regarding the role of OPN in MPMs derive from the marker's measurement in serum samples, most commercial laboratory kits for OPN assay are suitable only for measuring plasma levels, as indicated by the manufacturers. Our study aimed to evaluate the influence of preanalytic variables on serum and plasma OPN, to compare serum and plasma OPN in the same population, and to assess whether OPN levels can aid in the diagnostic distinction of patients with MPM versus benign respiratory disease (BRD) and healthy subjects exposed to asbestos. Methods The influence of preanalytic variables such as the length of storage at different temperatures and the number of thawings of samples on serum and plasma OPN measurements were evaluated. We measured OPN in 239 plasma samples from 207 asbestos-exposed subjects including 94 healthy controls and 113 subjects with BRD, and 32 patients with epithelial MPM, employing a commercially available ELISA. Serum OPN was measured in 196 of the same 239 samples from 80 healthy subjects, 92 BRD patients and 24 MPM patients. Results We found that both serum and plasma OPN levels were influenced by storage at –80°C and by the number of thawings, while serum OPN was influenced also by storage at room temperature. Plasma and serum OPN levels were significantly higher (p<0.0001) in patients with epithelial MPM than in the healthy control group and the BRD group. The application of a ROC curve for plasma OPN resulted in an AUC value of 0.780 with a best cutoff of 878.65 ng/mL, with a sensitivity of 68.8% and a specificity of 84.5%. The AUC for sOPN was 0.725 with a best cutoff of 16.06 ng/mL, with a sensitivity of 62.5% and a specificity of 87.3%. Within the control group no significant correlation was observed between age, duration of asbestos exposure, pack-years in current smokers, lung function or imaging parameters and plasma or serum OPN. Conclusions These data suggest that plasm OPN and serum OPN are not influenced by confounding factors such as age, smoking habits and asbestos exposure. Plasma and serum OPN may be useful markers in the diagnosis of epithelial MPM in addition to traditional radiological exams. However, in our opinion plasma OPN is preferable to serum OPN because it is more stable and measurements of OPN in serum are less reliable.

scholarly journals Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Danijela Strbac ◽  
Katja Goricar ◽  
Vita Dolzan ◽  
Viljem Kovac
Keyword(s):  
Matrix Metalloproteinases ◽  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Statistical Analyses ◽  
Baseline Risk ◽  
Categorical Variables ◽  
Control Group ◽  
Pleural Mesothelioma ◽  
Environment Interaction ◽  
Risk Predictors

Abstract Background Malignant mesothelioma (MM) is a rare disease, linked to asbestos exposure in more than 80% of the cases. Matrix metalloproteinases (MMPs) have been identified as modulators of the tumour microenvironment and carcinogenesis. Polymorphisms of selected MMPs have been studied as potential biomarkers of time to progression (TTP) and overall survival (OS) in MM. The aim of our study was to investigate selected MMP polymorphisms as baseline risk predictors in MM development in combination with other well known risk factors, such as asbestos exposure. Patients and methods The study included 236 patients and 161 healthy blood donors as the control group. Ten different polymorphisms in three MMP genes were genotyped using a fluorescence-based competitive allele-specific assay (KASPar): MMP2 rs243865, rs243849 and rs7201, MMP9 rs17576, rs17577, rs2250889 and rs20544, and MMP14 rs1042703, rs1042704 and rs743257. In statistical analyses continuous variables were described using median and range (25%–75%), while frequencies were used to describe categorical variables. Deviation from the Hardy-Weinberg equilibrium (HWE) was assessed using the standard chi-square test. The additive and dominant genetic models were used in statistical analyses. The association of genetic polymorphism with MM risk were examined by logistic regression to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Results Carriers of at least one polymorphic MMP2 rs243865 allele tended to have a decreased risk for MM (OR = 0.66, 95% CI = 0.44–1.00; P = 0.050). The association was more pronounced in patients with known asbestos exposure: carriers of at least one polymorphic allele had significantly lower MM risk (OR = 0.55, 95% CI = 0.35–0.86; P = 0.009). None of the other tested polymorphisms showed association with the risk of malignant pleural mesothelioma. Conclusions The MMP2 rs243865 polymorphism may have a protective role in malignant pleural mesothelioma development. This finding is even more evident in patients exposed to asbestos, implying a strong gene-environment interaction.

scholarly journals Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

2018 ◽  
Vol 52 (2) ◽  
pp. 160-166 ◽  
Author(s):  
Danijela Strbac ◽  
Katja Goricar ◽  
Vita Dolzan ◽  
Viljem Kovac
Keyword(s):  
Matrix Metalloproteinases ◽  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Statistical Analyses ◽  
Baseline Risk ◽  
Categorical Variables ◽  
Control Group ◽  
Pleural Mesothelioma ◽  
Environment Interaction ◽  
Risk Predictors

Abstract Background Malignant mesothelioma (MM) is a rare disease, linked to asbestos exposure in more than 80% of the cases. Matrix metalloproteinases (MMPs) have been identified as modulators of the tumour microenvironment and carcinogenesis. Polymorphisms of selected MMPs have been studied as potential biomarkers of time to progression (TTP) and overall survival (OS) in MM. The aim of our study was to investigate selected MMP polymorphisms as baseline risk predictors in MM development in combination with other well known risk factors, such as asbestos exposure. Patients and methods The study included 236 patients and 161 healthy blood donors as the control group. Ten different polymorphisms in three MMP genes were genotyped using a fluorescence-based competitive allele-specific assay (KASPar): MMP2 rs243865, rs243849 and rs7201, MMP9 rs17576, rs17577, rs2250889 and rs20544, and MMP14 rs1042703, rs1042704 and rs743257. In statistical analyses continuous variables were described using median and range (25%–75%), while frequencies were used to describe categorical variables. Deviation from the Hardy-Weinberg equilibrium (HWE) was assessed using the standard chi-square test. The additive and dominant genetic models were used in statistical analyses. The association of genetic polymorphism with MM risk were examined by logistic regression to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Results Carriers of at least one polymorphic MMP2 rs243865 allele tended to have a decreased risk for MM (OR = 0.66, 95% CI = 0.44–1.00; P = 0.050). The association was more pronounced in patients with known asbestos exposure: carriers of at least one polymorphic allele had significantly lower MM risk (OR = 0.55, 95% CI = 0.35–0.86; P = 0.009). None of the other tested polymorphisms showed association with the risk of malignant pleural mesothelioma. Conclusions The MMP2 rs243865 polymorphism may have a protective role in malignant pleural mesothelioma development. This finding is even more evident in patients exposed to asbestos, implying a strong gene-environment interaction.

The usefulness of biomarkers in diagnosis of asbestos-induced malignant pleural mesothelioma

2021 ◽  
pp. 096032712110173
Author(s):  
Zübeyde Tanrıverdi ◽  
Fatih Meteroglu ◽  
Hande Yüce ◽  
Abdurrahman Şenyiğit ◽  
Mümtaz Işcan ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Early Diagnosis ◽  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Diagnostic Value ◽  
Control Group ◽  
Pleural Mesothelioma ◽  
Spearman Correlation ◽  
Non Invasive ◽  
Noninvasive Markers

Introduction: Malignant pleural mesothelioma (MPM) is a malignant tumor that is associated mostly with asbestos exposure. The present study was to evaluates the diagnostic value of neopterin, periostin, YKL-40, Tenascin-C (TNC), and Indolamine 2,3-dioxygenase (IDO) as noninvasive markers of malign pleural mesothelioma. Methods: Included in the study were 30 patients diagnosed with malign pleural mesothelioma, and 25 people as a control group. Biomarker levels were determined using an enzyme immunoassay . A Mann-Whitney U test and Spearman correlation methods were used for the statistical analysis. Results: All evaluated biomarkers were found to be significantly higher in the MPM group than in the control group ( p < 0.05). There was no effect of such variables as gender, age or MPMsubtype on the parameters ( p > 0.05) in the patient group. All biomarkers were positively correlated with each other ( p < 0.001). Conclusions: The current non-invasive biomarkers that can be used in the diagnosis of MPM yielded significant results and can make important contributions to the early diagnosis of MPM.

scholarly journals Blocking the GITR-GITRL pathway to overcome resistance to therapy in sarcomatoid malignant pleural mesothelioma

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Meilin Chan ◽  
Licun Wu ◽  
Zhihong Yun ◽  
Trevor D. McKee ◽  
Michael Cabanero ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Malignant Pleural Mesothelioma ◽  
Neutralizing Antibodies ◽  
Pleural Mesothelioma ◽  
Spheroid Formation ◽  
Resistance To Therapy ◽  
Sarcomatoid Mesothelioma

AbstractMalignant pleural mesothelioma (MPM) is an aggressive neoplasm originating from the pleura. Non-epithelioid (biphasic and sarcomatoid) MPM are particularly resistant to therapy. We investigated the role of the GITR-GITRL pathway in mediating the resistance to therapy. We found that GITR and GITRL expressions were higher in the sarcomatoid cell line (CRL5946) than in non-sarcomatoid cell lines (CRL5915 and CRL5820), and that cisplatin and Cs-137 irradiation increased GITR and GITRL expressions on tumor cells. Transcriptome analysis demonstrated that the GITR-GITRL pathway was promoting tumor growth and inhibiting cell apoptosis. Furthermore, GITR+ and GITRL+ cells demonstrated increased spheroid formation in vitro and in vivo. Using patient derived xenografts (PDXs), we demonstrated that anti-GITR neutralizing antibodies attenuated tumor growth in sarcomatoid PDX mice. Tumor immunostaining demonstrated higher levels of GITR and GITRL expressions in non-epithelioid compared to epithelioid tumors. Among 73 patients uniformly treated with accelerated radiation therapy followed by surgery, the intensity of GITR expression after radiation negatively correlated with survival in non-epithelioid MPM patients. In conclusion, the GITR-GITRL pathway is an important mechanism of autocrine proliferation in sarcomatoid mesothelioma, associated with tumor stemness and resistance to therapy. Blocking the GITR-GITRL pathway could be a new therapeutic target for non-epithelioid mesothelioma.

The role of imaging in malignant pleural mesothelioma

2002 ◽  
Vol 29 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Edith M. Marom ◽  
Jeremy J. Erasmus ◽  
Harvey I. Pass ◽  
Edward F. Patz
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma

scholarly journals Identification of Redox-Sensitive Transcription Factors as Markers of Malignant Pleural Mesothelioma

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1138
Author(s):  
Martina Schiavello ◽  
Elena Gazzano ◽  
Loredana Bergandi ◽  
Francesca Silvagno ◽  
Roberta Libener ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Malignant Pleural Mesothelioma ◽  
Antioxidant Defense ◽  
Asbestos Exposure ◽  
Predictive Biomarkers ◽  
Antioxidant Systems ◽  
Pleural Mesothelioma ◽  
Related Factor ◽  
Aggressive Cancer

Although asbestos has been banned in most countries around the world, malignant pleural mesothelioma (MPM) is a current problem. MPM is an aggressive tumor with a poor prognosis, so it is crucial to identify new markers in the preventive field. Asbestos exposure induces oxidative stress and its carcinogenesis has been linked to a strong oxidative damage, event counteracted by antioxidant systems at the pulmonary level. The present study has been focused on some redox-sensitive transcription factors that regulate cellular antioxidant defense and are overexpressed in many tumors, such as Nrf2 (Nuclear factor erythroid 2-related factor 2), Ref-1 (Redox effector factor 1), and FOXM1 (Forkhead box protein M1). The research was performed in human mesothelial and MPM cells. Our results have clearly demonstrated an overexpression of Nrf2, Ref-1, and FOXM1 in mesothelioma towards mesothelium, and a consequent activation of downstream genes controlled by these factors, which in turn regulates antioxidant defense. This event is mediated by oxidative free radicals produced when mesothelial cells are exposed to asbestos fibers. We observed an increased expression of Nrf2, Ref-1, and FOXM1 towards untreated cells, confirming asbestos as the mediator of oxidative stress evoked at the mesothelium level. These factors can therefore be considered predictive biomarkers of MPM and potential pharmacological targets in the treatment of this aggressive cancer.

Experimental study of the inhibition effect of CXCL12/CXCR4 in malignant pleural mesothelioma

2018 ◽  
Vol 67 (2) ◽  
pp. 338-345 ◽  
Author(s):  
Jianshuang Li ◽  
Tong Li ◽  
Shuo Li ◽  
Lipeng Xie ◽  
Yi-Lin Yang ◽  
...  
Keyword(s):  
Treatment Group ◽  
Malignant Pleural Mesothelioma ◽  
Synergistic Effects ◽  
Control Group ◽  
Pleural Mesothelioma ◽  
Gene Expressions ◽  
Relationship Of ◽  
The Relationship ◽  
Cxcr4 Axis

Previous studies have demonstrated that CXCL12/CXCR4 axis is closely related to tumors such as malignant pleural mesothelioma (MPM). This research was conducted in order to detect whether CXCL12/CXCR4 inhibitors could restrain MPM and have a synergistic effect with chemotherapy, also to investigate the relationship of CXCL12/CXCR4 with other gene expressions in MPM. Forty mice were injected MPM cells and randomly divided into four groups: the PBS (control group), AMD3100 (CXCR4-CXCL12 antagonist), pemetrexed and AMD3100 plus pemetrexed. The mice were treated respectively for duration of 3 weeks. The size, bioluminescence and weight of tumors were measured. The differences between gene expressions in each group were analyzed. The tumor weights of each treatment group were lower than that of the control group (p<0.05). The bioluminescence of the tumor of the AMD3100 treatment group and the AMD3100 plus pemetrexed treatment group were lower than that of the control group (p<0.05), and AMD3100 was shown to have synergistic effects with pemetrexed (p<0.05). Among the 2.5 billion genes, several hundreds of genes expressed differently between groups. Results show that AMD3100 and pemetrexed can inhibit the growth of MPM in vivo, also that there is a better result if both are used together. Our findings suggest that CXCL12/CXCR4 axis affects a certain amount of gene expression in MPM.

scholarly journals Increased Standardised Incidence Ratio of Malignant Pleural Mesothelioma in Taiwanese Asbestos Workers: A 29-Year Retrospective Cohort Study

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Cheng-Kuan Lin ◽  
Yu-Ying Chang ◽  
Jung-Der Wang ◽  
Lukas Jyuhn-Hsiarn Lee
Keyword(s):  
Cohort Study ◽  
General Population ◽  
Incidence Rate ◽  
Malignant Pleural Mesothelioma ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Asbestos Exposure ◽  
Pleural Mesothelioma ◽  
Calendar Period ◽  
Incident Cases

Objective. This paper aimed to determine the standardised incidence ratio (SIR) of malignant pleural mesothelioma (MPM) in workers exposed to asbestos in Taiwan.Methods. All workers employed in asbestos-related factories and registered by the Bureau of Labour Insurance between 1 March, 1950, and 31 December, 1989, were included in the study and were followed from 1 January, 1980, through 31 December, 2009. Incident cases of all cancers, including MPM (ICD-9 code: 163), were obtained from the Taiwan Cancer Registry. SIRs were calculated based on comparison with the incidence rate of the general population of Taiwan and adjusted for age, calendar period, sex, and duration of employment.Results. The highest SIR of MPM was found for male workers first employed before 1979, with a time since first employment more than 30 years (SIR 4.52, 95% CI: 2.25–8.09). After consideration of duration of employment, the SIR for male MPM was 5.78 (95% CI: 1.19–16.89) for the workers employed for more than 20 years in asbestos-related factories.Conclusions. This study corroborates the association between occupational asbestos exposure and MPM. The highest risk of MPM was found among male asbestos workers employed before 1979 and working for more than 20 years in asbestos-related factories.

scholarly journals Studying the Role of C-Reactive Protein in Patients with Sleeve Gastrectomy in Baghdad

2021 ◽  
Vol 3 (1) ◽  
pp. 55-60
Author(s):  
Mohammed Abbas Fadil ◽  
Raya Ezat Maroof ◽  
Moayed Abbas Fadil
Keyword(s):  
Sleeve Gastrectomy ◽  
Healthy Person ◽  
Control Group ◽  
C Reactive Protein ◽  
Serum Samples ◽  
Reactive Protein ◽  
Medical City ◽  
Healthy Control ◽  
And Control

Obesity and severe obesity are increasing serious health problems with an epidemic percentage in most countries. In Sleeve gastrectomy, a part of the stomach structure is removed, limiting its capacity by about two to three. A total of thirty blood samples were collected from patients with obesity and the result was compared with healthy person throughout the time from November 2019 to September 2020. Before sleeve gastrectomy and after more than 6 months of sleeve surgery, the sample was collected from the Medical City/Baghdad Teaching Hospital, the withdrawal was again taken at home to have pre and post sleeve gastrectomy, Patient age ranged between [20-46] years for obese patients and healthy control. Then the serum samples were obtained from patients and control group to screen for C-reactive protein by agglutination method. The result of the present study found that the positivity of CRP in pre-operation is higher than that of post-operative with high significance [P<0.005].

scholarly journals Diagnostic role of immunocytochemistry in malignant pleural mesothelioma

Pathology ◽  
2016 ◽  
Vol 48 ◽  
pp. S136
Author(s):  
Lam Nguyen Son ◽  
Thanh Tran Dinh ◽  
Dung Nguyen Huy
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma ◽  
Diagnostic Role
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