Eun-Kee Park

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 find new candidate biomarkers for diagnosing early stage MM.

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.

The present study investigates renal inner medullary collecting duct (mIMCD3) cells and human embryonic kidney cells (HEK293) for evaluation of cytotoxicity of nephrotoxic compounds. The 24 h LC₅₀ values for cisplatin, paraquat and ibuprofen in mIMCD3 cells were 135, 155 and 3600 μM, respectively. The 24 h LC₅₀ values for paraquat and ibuprofen in HEK293 cells were 180 and 1000 μM, respectively. Effects of hyperosmolality on cytotoxicity of paraquat were additive in mIMCD3 cells. These data demonstrate that renal hyperosmolality has an additive effect on cytoxicity of paraquat.

Renal inner medullary collecting duct cells (mIMCD3) and human embryonic kidney cells (HEK293) were used for cytoscreening of thimerosal and mercury chloride (HgCl₂). Thimerosal and HgCl₂ acted in a concentration-dependent manner. In mIMCD3 cells the 24-h LC₅₀ values for thimerosal, thiosalicylic acid, 2,2-dithiosalicylic acid, and 2-sulfobenzoic acid were 2.9, 2200, >1000, and >10,000 μM, respectively. The 24-h LC₅₀ value for HgCl₂ in mIMCD3 cells was 40 μM. In HEK293 cells, the 24-h LC₅₀ value for thimerosal was 9.5 μM. These data demonstrate that the higher cytotoxicity produced by thimerosal on renal cells with respect to similar compounds without Hg may be related to this metal content. The present study also establishes mIMCD3 cells as a valuable model for evaluation of cytotoxicity of nephrotoxic compounds.