Clinical Chemistry and Laboratory Medicine

Our medical research library holds 9 studies published in Clinical Chemistry and Laboratory Medicine (2000–2012). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 7 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 1 study PubMed has no abstract for, we give the abstract printed in the article or, where there is none, a summary we wrote from it, each labeled as such.

About the journal

• Publisher: Walter De Gruyter
• Published: 1998 to the present, Germany
• Language: English
• ISSN: 1434-6621 (print), 1437-4331 (electronic)
• Continues: European Journal of Clinical Chemistry and Clinical Biochemistry
• Its record in the NLM Catalog

2010s

• A predictive equation to adjust for clinical variables in soluble mesothelin-related protein (SMRP) levels. E.K. Park, D. Wilson, D.H. Yates. 2012;50(12):2199-204. PubMed · Publisher

  Abstract

  Background: Malignant mesothelioma (MM) is an aggressive pleural tumor which is difficult to diagnose in its early stages. Thus, biomarkers for MM including soluble mesothelin-related protein (SMRP) are currently an area of intense research interest. However, SMRP is affected by several factors other than malignancy which need to be taken into account in the individual patient. This study aimed to evaluate factors required to adjust SMRP levels for such variables and produce a useful prediction equation for clinical application.

  Methods: Serum SRMP levels were measured in 535 subjects formerly exposed to asbestos and silica, including many with asbestos-related disorders (ARDs). Linear regression analyses were used to quantify the strength and “ direction ” of the relationship between SMRP and several independent variables,and 2 × 2 tables were used to determine the diagnostic accuracy of SMRP levels, taking into account clinical variables.

  Results: SMRP levels were affected by age and glomerular filtration rate (GFR), which were strong confounders in this study. Body mass index (BMI) was also an initial confounder but lost significance after other factors were taken into account.SMRP was also affected by smoking. Poor sensitivity (15.1 % )for SMRP values among subjects with non-malignant asbestos-related disorders was found when compared to currently healthy subjects with a history of asbestos exposure.

  Conclusions: The present study proposes an equation based on age and GFR to improve diagnostic accuracy of SMRP.The poor sensitivity of SMRP found in this study suggests that further work is needed to fi nd new candidate biomarkers for diagnosing early stage MM.

• Association of malignant mesothelioma and asbestos related conditions with ovarian cancer: shared biomarkers and a possible etiological link?. A.J. Rai, R.M. Flores. 2011;49(1):5-7. Comment · Editorial PubMed · Publisher

  Summary

  This editorial responded to a paper by Park et al. in the same journal issue, which suggested that benign asbestos-related pleural disease may share biomarkers with ovarian cancer. The authors compared malignant mesothelioma and ovarian cancer from biological and clinical perspectives. On the biological side, they summarised published gene expression and biomarker studies. These included one that identified 189 genes differentially expressed between ovarian cancer and mesothelioma effusions, with 13 validated by quantitative PCR. They also described work on MUC4, tenascin-X and folate receptor genes, and an intraperitoneal mouse tumour model expressing mesothelin. On the clinical side, they reported about 3,300 new mesothelioma cases and about 21,550 new ovarian cancer cases each year. The two tumours spread in similar sheet-like patterns with ascites or pleural fluid, look the same on imaging, and require biopsy to tell apart. WT-1 does not distinguish peritoneal mesothelioma from ovarian carcinoma. Ten-year ovarian cancer survival ranged from 84% (stage IA) to 11% (stage IIIC), while five-year mesothelioma survival was under 15%. Both are managed surgically by cytoreduction. The authors stated that mesothelioma is clearly linked to asbestos, while there is scant if any evidence linking asbestos to ovarian cancer. They concluded that the literature suggested a possible connection between mesothelioma and ovarian cancer subtypes. Extending this to benign asbestos-related conditions remained a hypothesis that was premature and needed further study.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

• Clinical significance of pleural effusion mesothelin in malignant pleural mesothelioma. S. Yamada, C. Tabata, R. Tabata, et al. 2011;49(10):1721-6. PubMed · Publisher

  Abstract

  Background: Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM has a limited response to conventional chemotherapy and radiotherapy, so early diagnosis of MPM is very important. This study investigated the pleural effusion mesothelin levels in patients with MPM and compared them to those of a population with a non-malignant pleuritis or lung cancer involving malignant pleural effusion.

  Methods: The pleural effusion mesothelin concentrations were measured in 45 MPM patients and 53 non-MPM individuals (24 individuals with non-malignant pleural effusions and 29 individuals with lung cancer involving malignant pleural effusion).

  Results: This study demonstrated that patients with MPM had significantly higher pleural effusion mesothelin levels than a population with non-malignant pleuritis or lung cancer involving malignant pleural effusion. The difference in overall survival between the groups with pleural effusion mesothelin levels lower and higher than the assumed cut-off of 10 nM was significant.

  Conclusions: The data suggest that the pleural effusion mesothelin concentration could be useful as an aid for the diagnosis of MPM.

• Evaluation of ovarian cancer biomarkers in subjects with benign asbestos-related pleural diseases. E.K. Park, A.R. Johnson, D.H. Yates, et al. 2011;49(1):147-50. PubMed · Publisher

  Abstract

  Background: Mesothelioma and ovarian cancer have been reported to have a similar pathogenesis, and for this reason it was hypothesized that there may be biomarkers in common and possibly associated with benign pleural diseases caused by asbestos exposure.

  Methods: Serum biomarkers including insulin-like growth factor-II (IGF-II), leptin, prolactin and vascular endothelial growth factor (VEGF) were measured in an observational study of subjects with benign asbestos-related pleural diseases (BARPD) (n=24) and healthy subjects with an asbestos exposure history (n=12).

  Results: Mean serum IGF-II and VEGF concentration in healthy subjects with a history of asbestos exposure were higher than those with BARPD. Mean serum concentrations of leptin and prolactin showed opposite trends when compared to IGF-II and VEGF concentrations among these groups.

  Conclusions: The results suggest that IGF-II and VEGF concentrations are lower in BARPD, similar to studies of ovarian cancer. This finding warrants further investigation with malignant asbestos-related diseases.

• Biomarkers for early detection of mesothelioma in asbestos-exposed subjects. E.K. Park, P.S. Thomas, D.H. Yates. 2010;48(11):1673-4. Letter PubMed · Publisher

• Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population. E.K. Park, P.S. Thomas, J. Creaney, et al. 2010;48(6):869-74. PubMed · Publisher

  Abstract

  Background: Soluble mesothelin-related protein (SMRP) is increased in the sera of patients with malignant mesothelioma (MM), and has been suggested as a diagnostic tool for MM in an asbestos exposed population. However, factors affecting SMRP concentrations in normal subjects and those with other asbestos related disorders have not been investigated in any large population based study.

  Methods: Five hundred and thirty-eight subjects with a history of asbestos exposure were studied. Age, height, weight, body mass index (BMI), serum creatinine and glucose, estimated glomerular filtration rate (eGFR) and lung function were compared with SMRP concentrations.

  Results: The mean age [+/- standard deviation (SD)] of participants was 66.9 (+/-10.1) years, and mean (+/-SD) serum SMRP concentration was 0.91 (+/-0.67) nmol/L. SMRP values were inversely associated with weight (Pearson r=-0.1254, p=0.0036), BMI (Pearson r=-0.1594, p=0.0002), blood glucose (Pearson r=-0.1515, p=0.0004), single-breath carbon monoxide diffusing capacity (DLco) % predicted (Pearson r=-0.1847, p<0.0001), eGFR (Pearson r=-0.2835, p<0.0001) and single-breath carbon monoxide diffusing capacity per unit alveolar volume (DLco/VA)% predicted (Pearson r=-0.1872, p<0.0001) but were positively associated with age (Pearson r=0.2315, p<0.0001) and creatinine (Pearson r=0.3833, p<0.0001).

  Conclusions: This study has shown that demographic variables, physiological factors and lung function are associated with serum SMRP concentrations. Confounding factors should be considered when interpreting serum SMRP.

• Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers for malignant mesothelioma: analytical validation of ELISA based assays and characterization at mRNA and protein levels. A.J. Rai, R.M. Flores, A. Mathew, et al. 2010;48(2):271-8. PubMed · Publisher

  Abstract

  Background: There is a need to identify reliable markers for malignant mesothelioma. Soluble mesothelin related peptides (SMRP) and osteopontin (OPN) have gained interest in recent years for this purpose.

  Methods: SMRP (Fujirebio Diagnostics Inc.) and OPN (R&D Inc.) ELISA methods were evaluated for multiple parameters. Concentrations were measured in blood from patients with mesothelioma, normal healthy volunteers, and patients with other (non-mesothelioma) cancers. In silico analysis was performed using the GeoProfiles database. At the protein level, SMRP and OPN were measured in cell culture supernatants, and values were compared in patients pre- and post-extrapleural pneumonectomy.

  Results: The SMRP assay demonstrates intra-assay CVs of 2.3% and 3% (at 4.6 nM and 13.7 nM, respectively), and inter-assay CVs of 3.5% and 3.7% at the same concentrations. The limit of detection (LOD) is 0.182 nM. The OPN assay demonstrates intra-assay CVs of 5.8%, 4.1%, and 5.2% (at 1.9, 5.1, and 11.1 ng/mL, respectively), and inter-assay CVs of 8.5%, 8.4%, and 12.1% at the same concentrations. The LOD is 0.032 ng/mL. Both SMRP and OPN in mesothelioma patients were significantly higher than in patients with other (non-mesothelioma) cancer and in healthy volunteers. The two markers do not appear to correlate with each other and exhibit different tissue expression patterns. Protein concentrations of these markers are highest in different sets of cell lines. Finally, SMRP but not OPN concentrations were decreased in five of seven consecutive patients after extrapleural pneumonectomy, compared to their respective pre-operative values.

  Conclusions: These assays provide reliable and reproducible quantitation of SMRP and OPN proteins. Both are increased in mesothelioma patients compared to non-mesothelioma controls. However, the two analytes do not correlate with each other and show distinct expression profiles and protein expression. Concentrations of SMRP but not OPN are decreased in post-surgical samples. Our results further characterize these markers, establish assay performance characteristics, and lay the groundwork for further studies to measure these markers in blood.

2000s

• Mesothelin family proteins and diagnosis of mesothelioma: analytical evaluation of an automated immunoassay and preliminary clinical results. F. Di Serio, A. Fontana, M. Loizzi, et al. 2007;45(5):634-8. PubMed · Publisher

  Abstract

  Background: Studies have suggested that soluble mesothelin-related protein (SMRP) can be used as a serum marker of malignant mesothelioma.

  Methods: We assessed the analytical performance of the Mesomark (Fujirebio Diagnostic) two-step ELISA on an automated analyser and performed a preliminary clinical evaluation. The precision of the assay and the in vitro effect of interfering substances on SMRP concentrations were investigated. The serum marker was analysed in 109 healthy subjects never exposed to asbestos, 26 healthy subjects exposed to asbestos, 33 patients with asbestosis, 33 with asbestos-related pleural plaques, 10 with non-malignant pleural diseases, 30 with lung cancer and 24 with histological diagnosis of pleural mesothelioma.

  Results: Using the International Mesothelioma Interest Group classification, there were nine stage IV, two stage III, four stage II and nine stage I patients. SMRP concentrations of 4.75, 11.0 and 14 nmol/mL showed a total imprecision of 3.5%, 3.1% and 3.8%. The detection limit was 0.035 nmol/mL; the mean SMRP concentration of 0.63 nmol/mL was associated with a coefficient of variation of 10%. There was no effect (p>0.05) of interfering substances. Serum samples from patients with established pleural mesothelioma had significantly higher (p<0.05) concentrations of SMRP than control healthy and patient groups.

  Conclusions: SMRP measured on automated systems could be useful for the diagnosis of mesothelioma in routine clinical practice.

• Serum ras (p21) as a marker for occupationally derived lung cancer?. J. Schneider, P. Presek, A. Braun, et al. 2000;38(4):301-5. PubMed · Publisher

  Abstract

  Certain subsets of the population are especially sensitive to carcinogens, and this can be determined using molecular biological methods. In the literature there has been evidence presented for the use of p21ras (ras) as a tumor marker for human carcinogenic substances such as asbestos, polycyclic aromatic hydrocarbons, and vinyl chloride in the workplace. In this study we have examined whether serum ras could serve as a biomarker for the early detection of occupationally derived lung cancer, with an emphasis on Schneeberger (radon-induced) lung cancer. Sera were taken from 65 male tumor patients. Fifty-nine patients suffered from primary lung cancer (including 18 patients with Schneeberger lung cancer and 12 patients with asbestos-related lung cancer). Additionally, 29 patients with non-malignant lung disease, and a healthy control group (44) including 32 former uranium miners of SDAG Wismut exposed to ionizing radiation (radon and its decay products) were examined. Ras protein was determined via three different methods: 1) immunoprecipitation followed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting; 2) SDS-PAGE using 5-17% gradient gels followed by Western blotting; 3) pre-incubation with Blue Sepharose, SDS-PAGE on 5-17% gradient gels, and Western blotting. The results show that 1 ng ras protein was measurable in serum standards. This protein could not be detected in patient sera or in sera from any of the study groups. Thus, ras cannot be considered useful as a marker for the early detection of asbestos-induced or Schneeberger lung cancer.

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