c-Met receptor tyrosine kinase (RTK) has not been extensively studied in malignant pleural mesothelioma

Purpose: High levels of serum-soluble mesothelin family proteins (SMRP) have been found to be associated with malignant mesothelioma (MM), but not lung cancer (LC).To verify the clinical role of this marker for both these tumors, we tested serum SMRP in the largest population of thoracic cancers ever assembled. Experimental Design: SMRP blood concentrations were measured in 107 patients with MM, 215 patients with LC, 130 patients with benign respiratory diseases (BRD), and 262 controls. Statistical comparison between mean serum SMRP levels in all groups was done and receiver operating characteristic curves were constructed to evaluate the performance of this marker. Results: SMRP levels were significantly higher in patients with MM and LC than in patients with benign respiratory diseases and controls (P < 0.001). The area under the receiver operating characteristic curve for serum SMRP discriminating MM and controls was 0.77 (95% confidence interval, 0.71-0.83), with a best cutoff of 1.00 nmol/L (sensitivity, 68.2%; specificity, 80.5%). In both MM and LC, serum SMRP levels did not differ significantly between early and late stages. High SMRP levels proved to be an independent negative prognostic factor in patients with MM. Conclusions: Our data confirm that serum SMRP is a promising marker for the diagnosis, prognosis, and clinical monitoring of MM.We found that serum SMRP dosage may prove helpful in LC diagnosis as well.These data may also have positive repercussions on secondary preventive medical strategies for workers previously exposed to asbestos.

Objectives: The body adiposity index (BAI) is a proposed alternative to the body mass index (BMI) that has shown good cross‐sectional agreement with percent body fat (%BF) in validation studies. The objective of this study was to examine the ability of BAI to track adiposity change over time in a biracial sample of midlife women. Methods: African‐American (n = 159) and Caucasian (n = 206) women, aged 42–60 years, at the Chicago site of the Study of Women's Health Across the Nation were followed from 2002 to 2008. BAI and BMI were calculated from measurements taken at annual assessments. %BF was quantified using whole‐body dual‐energy X‐ray absorptiometry. Difference scores (BAIΔ, BMIΔ, and %BFΔ) quantified adiposity change over a mean of 1.6 (SD = 0.7) years. Lin's concordance correlation (ρc) and Bland–Altman limits‐of‐agreement assessed agreement between BAI and %BF. Results: In examining adiposity change, BAIΔ showed poor agreement with %BFΔ in the overall sample (ρc = 0.41), African‐American women (ρc = 0.36), and Caucasian women (ρc = 0.43). BAIΔ estimated %BFΔ with minimal bias (+0.4%) but low precision (±6.3%BF limits‐of‐agreement). %BFΔ had weaker correlations with BAIΔ (rs = 0.38–0.48) than with BMIΔ (rs = 0.48–0.59). BAI and BMI showed similar cross‐sectional associations with %BF in the overall sample and within each race (rs > 0.74). Conclusions: We conclude that BAI is less accurate than BMI in tracking adiposity change in midlife women, and would not be a suitable replacement for BMI in most research applications involving adiposity change. Am. J. Hum. Biol., 2012. © 2012 Wiley Periodicals, Inc.

Nicotinic acetylcholine receptors (nAChR) are expressed on normal bronchial epithelial and nonsmall cell lung cancer (NSCLC) cells and are involved in cell growth regulation. Nicotine induced cell proliferation. The purpose of this study was to determine if interruption of autocrine nicotinic cholinergic signaling might inhibit A549 NSCLC cell growth. For this purpose α‐Cobratoxin (α‐CbT), a high affinity α7‐nAChR antagonist was studied. Cell growth decrease was evaluated by Clonogenic and MTT assays. Evidence of apoptosis was identified staining cell with Annexin‐V/PI. Characterization of the basal NF‐κB activity was done using the Trans‐AM NF‐κB assay colorimetric kit. “In vivo” antitumour activity was evaluated in orthotopically transplanted nude mice monitored by In vivo Imaging System technology. α‐CbT caused concentration‐dependent cell growth decrease, mitochondrial apoptosis caspases‐9 and 3‐dependent, but caspase‐2 and p53‐independent and down‐regulation of basal high levels of activated NF‐κB. α‐CbT treatment determines a significant reduction of tumor growth in nude mice orthotopically engrafted with A549‐luciferase cells (4.6% of living cells vs. 31% in untreated mice). No sign of toxicity was reported related to treatment. These findings suggest that α7‐nAChR antagonists namely α‐CbT may be useful adjuvant for treatment of NSCLC and potentially other cancers. © 2007 Wiley‐Liss, Inc.

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