Laura Moro

Publications (33) View all

• Article: PARP11 inhibition affects pleural mesothelioma cell viability and uncouples AKT/mTOR axis via SIRT1.

  Giulia Pinton, Arcangela Gabriella Manente, Bruno Murer, Elvira De Marino, Luciano Mutti, Laura Moro
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  ABSTRACT: Malignant Pleural Mesothelioma (MMe) is a rare but increasingly prevalent, highly aggressive cancer with poor prognosis. The aetiology of MMe is essentially a function of previous exposure to asbestos fibres, which are considered to be an early-stage carcinogen. Asbestos is toxic to human mesothelial cells (HMCs), that activate the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP1) to repair DNA. The targeting of PARP1 is showing considerable potential for delivering selective tumour cell kill while sparing normal cells, and offers a scientifically rational clinical application. We investigated PARP1 expression in normal mesothelial and MMe tissues samples. Immunohistochemical analysis revealed low PARP1 staining in peritumoural mesothelium. As opposite, a progressive increase in epithelioid and in the most aggressive sarcomatoid MMe tissues was evident. In MMe cell lines, we correlated increased PARP1 expression to sensitivity to its inhibitor CO-338 and demonstrated that CO-338 significantly reduced cell viability as single agent and was synergistic with cis-platin. Interestingly, we described a new correlation between PARP1 and the AKT/mTOR axis regulated by SIRT1. SIRT1 has a role in the modulation of AKT activation and PARP1 has been described to be a gatekeeper for SIRT1 activity by limiting NAD+ availability. Here, we firstly demonstrate an inverse correlation between AKT acetylation and phosphorylation modulated by SIRT1 in MMe cells treated with CO-338. In conclusion, this study demonstrates that PARP1 overexpression defines increased responsiveness to its inhibition, then these results imply that a substantial fraction of patients could be candidates for therapy with PARP inhibitors.
  Journal of Cellular and Molecular Medicine 01/2013; · 4.13 Impact Factor
• Source

  Available from: Alberto Minassi

  Dataset: Flavonoid-induced autophagy in hormone sensitive breast cancer cells.

  Elisa Brunelli, Giulia Pinton, Paolo Bellini, Alberto Minassi, Giovanni Appendino, Laura Moro
• Article: perifosine

  Giulia Pinton, Arcangela Gabriella Manente, Giovanni Angeli, Luciano Mutti, Laura Moro
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  ABSTRACT: Background: PI3K/AKT signalling pathway is aberrantly active and plays a critical role for cell cycle progression of human malignant pleural mesothelioma (MMe) cells. AKT is one of the important cellular targets of perifosine, a novel bioavailable alkylphospholipid that has displayed significant anti-proliferative activity in vitro and in vivo in several human tumour model systems and is currently being tested in clinical trials. Methods: We tested Perifosine activity on human mesothelial cells and different mesothelioma cell lines, in order to provide evidence of its efficacy as single agent and combined therapy. Results: We demonstrate here that perifosine, currently being evaluated as an anti-cancer agent in phase 1 and 2 clinical trials, caused a dose-dependent reduction of AKT activation, at concentrations causing MMe cell growth arrest. In this study we firstly describe that MMe cells express aside from AKT1 also AKT3 and that either the myristoylated, constitutively active, forms of the two proteins, abrogated perifosine-mediated cell growth inhibition. Moreover, we describe here a novel mechanism of perifosine that interferes, upstream of AKT, affecting EGFR and MET phosphorylation. Finally, we demonstrate a significant increase in cell toxicity when MMe cells were treated with perifosine in combination with cisplatin. Conclusions: This study provides a novel mechanism of action of perifosine, directly inhibiting EGFR/MET-AKT1/3 axis, providing a rationale for a novel translational approach to the treatment of MMe.
  PLoS ONE 05/2012; · 4.09 Impact Factor
• Article: Circulating tumor cells as a diagnostic test for malignant pleural mesothelioma.

  Giulia Pinton, Arcangela Gabriella Manente, Laura Moro, Luciano Mutti
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  ABSTRACT: The detection of circulating tumor cells (CTCs) may have important prognostic and therapeutic implications; therefore, we expect a broader range of tumor types in which CTC detection and count will routinely be conducted in the coming years. This article evaluates the application of CTC as a potentially useful diagnostic and prognostic test in malignant pleural mesothelioma (MMe). MMe is a rare but increasingly prevalent, highly aggressive asbestos exposure-related tumor. MMe develops after long time latency, is rarely diagnosed at early stages, is poorly sensitive to conventional treatments and presents a very short survival upon diagnosis. Pursuing research of CTC in MMe can represent a very important task for all the clinical and preclinical scientists working on blood biomarkers of this tumor. Possibly in combination with other diagnostic tools, such as a thoracoscopy and advanced imaging, CTC can represent a promising tool for MMe prognosis and follow-up. Further studies to confirm value of CTC test in MMe are warranted.
  Expert Opinion on Medical Diagnostics 05/2012; 6(3):171-173.
• Article: Circulating tumor cells as a diagnostic test for malignant pleural mesothelioma

  Giulia Pinton, Arcangela Gabriella Manente, Laura Moro†, Luciano Mutti
  Expert Opin. Med. Diagn. 03/2012;