18 research outputs found

    Epiregulin and EGFR interactions are involved in pain processing

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    The EGFR belongs to the well-studied ErbB family of receptor tyrosine kinases. EGFR is activated by numerous endogenous ligands that promote cellular growth, proliferation, and tissue regeneration. In the present study, we have demonstrated a role for EGFR and its natural ligand, epiregulin (EREG), in pain processing. We show that inhibition of EGFR with clinically available compounds strongly reduced nocifensive behavior in mouse models of inflammatory and chronic pain. EREG-mediated activation of EGFR enhanced nociception through a mechanism involving the PI3K/AKT/mTOR pathway and matrix metalloproteinase-9. Moreover, EREG application potentiated capsaicin-induced calcium influx in a subset of sensory neurons. Both the EGFR and EREG genes displayed a genetic association with the development of chronic pain in several clinical cohorts of temporomandibular disorder. Thus, EGFR and EREG may be suitable therapeutic targets for persistent pain conditions

    Additional diagnostic value of tumor markers in cytological fluid for diagnosis of non-small-cell lung cancer

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    <p>Abstract</p> <p>Background</p> <p>Cytological fluid from a needle aspiration biopsy (NAB) is obtained directly from tumor tissue, therefore many biomarker candidates will be present in high concentrations. The aim of this study was to prospectively assess and validate the tumor markers CYFRA 21–1, CEA, and SCC in cytological fluid obtained from NAB samples to determine if they improved the performance of NAB for diagnosing non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>A total of 194 patients (M:F = 128:66, mean age 63.7 years) with suspected malignant pulmonary lesions were prospectively enrolled and underwent percutaneous NAB. Levels of CYFRA 21–1, CEA, and SCC were measured by immunoassay in serum and cytological fluid obtained during aspiration biopsy. Cut-off values to determined malignancy were 3.3 ng/mL in serum and 15.7 ng/mL in cytological fluid for CYFRA 21–1, 5 ng/mL and 0.6 ng/mL for CEA, and 2 ng/mL and 0.86 ng/mL for SCC.</p> <p>Results</p> <p>Of 194 patients, 139 patients (71.6%) had NSCLC and 55 (28.4%) had benign lesions. Sensitivity increased significantly for NAB combined with cytological tumor markers compared with NAB alone (CYFRA 21–1: 95% versus 83.5%, p < 0.001, CEA: 92.1% versus 83.5%, p = 0.002, SCC: 91.4% versus 83.5%, p = 0.003). Accuracy improved significantly for NAB combined with cytological CYFRA 21–1 compared with NAB alone (95.9% versus 88.1%, p < 0.001). The area under curve (AUC) of NAB with cytological CYFRA 21–1 was significantly larger than for NAB alone (0.966 versus 0.917, p = 0.009).</p> <p>Conclusion</p> <p>Of the tested tumor markers, cytological fluid measurements of CYFRA 21–1 improved the diagnostic performance of NAB for NSCLC.</p
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