دورية أكاديمية
Induction of senescence markers after neo-adjuvant chemotherapy of malignant pleural mesothelioma and association with clinical outcome: An exploratory analysis
| العنوان: | Induction of senescence markers after neo-adjuvant chemotherapy of malignant pleural mesothelioma and association with clinical outcome: An exploratory analysis |
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| المؤلفون: | Sidi R., Pasello G., Opitz I., Soltermann A., Tutic M., Rehrauer H., Weder W., Stahel R. A., Felley-Bosco E. |
| المساهمون: | Sidi, R., Pasello, G., Opitz, I., Soltermann, A., Tutic, M., Rehrauer, H., Weder, W., Stahel, R. A., Felley-Bosco, E. |
| سنة النشر: | 2011 |
| المجموعة: | Padua Research Archive (IRIS - Università degli Studi di Padova) |
| مصطلحات موضوعية: | Accelerated senescence, Apoptosi, Clinical outcome, DNA-damaging chemotherapy, Malignant pleural mesothelioma, PAI-1, Senescence marker, Adult, Aged, Antineoplastic Combined Chemotherapy Protocol, Biomarkers, Tumor, Chemotherapy, Adjuvant, DNA Damage, Disease-Free Survival, Female, Human, Immunohistochemistry, Male, Mesothelioma, Middle Aged, Plasminogen Activator Inhibitor 1, Pleural Neoplasm, Treatment Outcome |
| الوصف: | The aim of this study was to assess the induction of senescence markers versus apoptosis pathways in malignant pleural mesothelioma (MPM) tumour samples before and after neo-adjuvant platinum-based chemotherapy and to investigate their relationship with clinical outcome. Specific senescence pathways were assessed by quantifying the expression of p21 and plasminogen activator inhibitor-1 (PAI-1) for the p21-p53 pathway, IGFBP7 for the IGF pathway and ALDH1A3 for the IFN pathway. p21 and PAI-1 expression were also assessed by immunohistochemistry. In addition, beta-galactosidase activity staining at pH 6.0 was performed. Apoptosis was determined by TUNEL assay. Clinical outcome was assessed by modified RECIST criteria, progression-free and overall survival. In a training set (n = 9 patients) paired comparison demonstrated a significant increase in p21 (p < 0.05), PAI-1 (p < 0.01) and apoptosis (p < 0.01) after neo-adjuvant chemotherapy. The patients with the highest increase in PAI-1 had stable disease, whilst patients with little change in senescence markers accompanied by a high increase in apoptosis had an objective response after chemotherapy. The hypothesis that stable disease might be associated with an increase in senescence markers was confirmed in a tissue microarray (n = 26 patients) using p21 and PAI-1 immunohistochemistry as readouts. For patients where survival and time to progression data were available, increased PAI-1 levels were significantly associated with a worst outcome. Our results demonstrate induction of senescence markers by neo-adjuvant chemotherapy in a proportion of patients with MPM and its potential association with a poor outcome. © 2010 Elsevier Ltd. All rights reserved. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/21036600; info:eu-repo/semantics/altIdentifier/wos/WOS:000286715800020; volume:47; issue:2; firstpage:326; lastpage:332; numberofpages:7; journal:EUROPEAN JOURNAL OF CANCER; http://hdl.handle.net/11577/3368205Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-78650713936 |
| DOI: | 10.1016/j.ejca.2010.09.044 |
| الإتاحة: | https://doi.org/10.1016/j.ejca.2010.09.044Test http://hdl.handle.net/11577/3368205Test |
| رقم الانضمام: | edsbas.BC9D36BF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.ejca.2010.09.044 |
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