Malignant Pleural Mesothelioma
ABSTRACT Malignant pleural mesothelioma (MPM) is a deadly disease that occurs in 2,000 to 3,000 people each year in the United States. Although MPM is an extremely difficult disease to treat, with the median overall survival ranging between 9 and 17 months regardless of stage, there has been significant progress over the last few years that has reshaped the clinical landscape. This article will provide a comprehensive discussion of the latest developments in the treatment of MPM. We will provide an update of the major clinical trials that impact mesothelioma treatment in the resectable and unresectable settings, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. In addition, there are controversial issues, such as the role of extrapleural pneumonectomy, adjuvant radiotherapy, and use of intensity-modulated radiotherapy versus hemithoracic therapy that will also be addressed in this manuscript.
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ABSTRACT: Osteopontin has been viewed as a promising biomarker for malignant pleural mesothelioma (MPM); however, the conclusions of various studies on diagnostic accuracy of osteopontin have not been consistent. The aim of this study was to conduct a systematic review and meta-analysis to evaluate the diagnostic accuracy of circulating osteopontin for MPM. Using appropriate key words, scientific literature that evaluated circulating levels of osteopontin for the diagnosis of MPM was retrieved from electronic databases. Only articles published in English till March 26, 2013 were included in this study. The quality of the studies was assessed using the revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tools. The random-effects models were applied for analysing the performance of pooled characteristics. Six studies were included in the analysis. The overall diagnostic sensitivity and specificity were 0.65 (95%CI: 0.60-0.70) and 0.81 (95%CI: 0.78-0.85), respectively. The area under summary receiver operating characteristic (sROC) curves (AUC) was 0.83. The diagnostic accuracy of serum and plasma osteopontin was comparable. Osteopontin is an effective marker for MPM diagnosis. However, more studies with a larger sample size and better design are needed to rigorously assess the diagnostic power of osteopontin.Clinica chimica acta; international journal of clinical chemistry 03/2014; 433. DOI:10.1016/j.cca.2014.02.024 · 2.76 Impact Factor
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ABSTRACT: Malignant mesothelioma (MM) is a highly aggressive tumor of the serous membranes for which there is currently no effective curative modality. Recent data suggest that hyperactivation of the tyrosine kinase SRC has a key role in MM development and therefore this kinase represents an important molecular target for MM therapy. We tested new pyrazolo[3,4-d]pyrimidine SRC inhibitors on a panel of MM cell lines expressing the active form of SRC. These SRC inhibitors exerted a significant proapoptotic effect on MM cells without affecting the normal mesothelial cell line MET-5A, supporting a possible use of these SRC inhibitors for a safe treatment of MM. We also showed that SRC inhibitor-induced apoptosis occurred concomitantly with an increase in the nuclear stability of the cyclin-dependent kinase inhibitor p27. This finding is remarkable considering that loss of nuclear p27 expression is a well-established adverse prognostic factor in MM, and p27 nuclear localization is crucial for its tumor-suppressive function. Consistently, SRC inhibition seems to promote the increase in p27 nuclear level also by inactivating the AKT kinase and downregulating cyclin D1, which would otherwise delay p27 nuclear import and provoke its cytoplasmic accumulation. To determine whether p27 stabilization has a direct role in apoptosis induced by SRC inhibition, we stably silenced the CDKN1B gene, encoding p27, in MSTO-211H and REN mesothelioma cells by transduction with lentiviral vectors expressing short hairpin RNAs against the CDKN1B transcript. Strikingly, p27 silencing was able to suppress the apoptosis induced by these SRC inhibitors in both MM cell lines, suggesting that p27 has a crucial proapoptotic role in MM cells treated with SRC inhibitors. Our findings reveal a new mechanism, dependent on p27 nuclear stabilization, by which SRC inhibition can induce apoptosis in MM cells and provide a new rationale for the use of SRC inhibitors in MM therapy.Oncogene 07/2011; 31(7):929-38. DOI:10.1038/onc.2011.286 · 8.56 Impact Factor
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ABSTRACT: A 77-year-old male patient with unresected malignant pleural mesothelioma, clinical stage T3N0M0 according to the New International Staging System for Diffuse Malignant Pleural Mesothelioma, received intensity-modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) after 6 cycles of chemotherapy with cisplatin and pemetrexed. SIB-IMRT delivered 40.5 Gy (1.5 Gy/fraction) to the left pleura and 50 Gy (1.85 Gy/fraction) to the sites of macroscopic disease. Radiotherapy was well tolerated. Two months after the end of radiotherapy the patient showed grade 2 lung toxicity (febrile episodes accompanied by dry cough) that was successfully treated with steroid therapy. Local control lasted for 2 years after SIB-IMRT. Then the tumor recurred marginally to the radiation field and the patient underwent chemotherapy with pemetrexed. Three years from the diagnosis, the patient is alive and in good general condition. He only takes prednisone 5 mg/daily for exertional dyspnea. To the best of our knowledge this is the first reported use of SIB-IMRT in unresected malignant pleural mesothelioma. Considering the dosimetric advantages of SIB-IMRT and the clinical results observed in our patient, additional evaluation of this technique seems justified.Tumori 96(4):618-22. · 1.09 Impact Factor