Publications (4)11.96 Total impact
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Article: Decreased expression of autophagic beclin 1 protein in idiopathic pulmonary fibrosis fibroblasts.
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ABSTRACT: Autophagy is the main cellular pathway for degradation of long-lived proteins and organelles and regulates cell fate in response to stress. Beclin 1 is a key regulator of this process. In some settings autophagy and apoptosis seems to be interconnected. Recent reports indicate that fibroblasts in idiopathic pulmonary fibrosis (IPF) acquire resistance to apoptosis. Here we examined the expression of beclin 1, and of the anti apoptotic protein Bcl-2 in human IPF fibroblasts using immunohistochemistry and molecular biology in both bioptic sections, in primary cultured of fibroblasts taken from patients with IPF and in fibroblast cell lines. Expression of beclin 1 and in fibroblasts from IPF was down-regulated in comparison with fibroblasts from normal lungs while the anti-apoptotic protein Bcl-2 expression was over-expressed. Treatment of fibroblasts cell cultures with cisplatin induced a significant increase in beclin 1, and caspase 3 protein levels but a reduction in Bcl-2 expression. These observations were confirmed by the analysis of acid compartments and transmission electron microscopy. Our results demonstrate a modified expression of the apoptotic beclin1 and of the oncogene Bcl-2 proteins in human IPF fibroblasts suggesting the existence of an autophagy/apoptosis system dysfunction. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.Journal of Cellular Physiology 12/2012; · 3.87 Impact Factor -
Article: WT1 CpG islands methylation in human lung cancer: A pilot study.
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ABSTRACT: CpG island hypermethylation of gene promoters and regulatory regions is a well-known mechanism of epigenetic silencing of tumor suppressors and is directly linked to carcinogenesis. Wilm's tumor gene (WT1) is a tumor suppressor protein involved in the regulation of human cell growth and differentiation and a modulator of oncogenic K Ras signaling in lung cancer. Changes in the pattern of methylation of the WT1 gene have not yet been studied in detail in human lung cancer. In this study we compared the methylation profile of WT1 gene in samples of neoplastic and non-neoplastic lung tissue taken from the same patients. DNA was extracted from neoplastic and normal lung tissue obtained from 16 patients with non small cell lung cancer (NSCLC). The methylation status of 29 CpG islands in the 5' region of WT1 was determined by pyrosequencing. Statistical analysis was carried out by T test and Mann Whitney test. The mean percentage of methylation, considering all CpG islands of WT1 in the neoplastic tissues of the 16 NSCLC patients, was 16.2±3.4, whereas in the normal lung tissue from the same patients it was 5.6±1.7 (p<0.001). Adenocarcinomas presented higher methylation levels than squamous cell carcinomas (p<0,001). Methylation of WT1 gene is significantly increased in NSCLC. Both histotype and exposure to cigarette smoke heavily influence the pattern of CpG islands which undergo hypermethylation.Biochemical and Biophysical Research Communications 08/2012; 426(3):306-9. · 2.48 Impact Factor -
Article: Homeodomain-interacting protein kinase2 in human idiopathic pulmonary fibrosis.
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ABSTRACT: Homeodomain-interacting protein kinase 2 (Hipk2) is an emerging player in cell response to genotoxic agents that contributes to the cell's decision between cell cycle arrest or apoptosis. HIPK2 acts as co-regulator of an increasing number of transcription factors and modulates many different basic cellular processes such as apoptosis, proliferation, DNA damage response, differentiation. Idiopathic pulmonary fibrosis (IPF) is characterized by an anatomical disarrangement of the lung due to fibroblast proliferation, extracellular matrix deposition and lung function impairment. Although the role of inflammation is still debated, attention has been focused on lung cell functions as fibroblast phenotype and activity. Aim of the present study was to analyze the loss of heterozygosity (LOH) at HIPK2 locus 7q32.34 in human lung fibroblasts and the HIPK2 expression in 15 IPF samples and in four primary fibroblast cell cultures isolated from IPF biopsies using semi-quantitative RT-PCR, Western blots and immunohistochemistry. We demonstrated a frequency of LOH in IPF fibroblasts of 46% for the internal D7S6440 microsatellite and 26.6% for the external D7S2468 microsatellite. Furthermore, we demonstrated low HIPK2 protein expression in those fibroblasts from IPF patients that present the HIPK2 LOH. The restoration of HIPK2 expression in IPF derived cells induced a significant reduction of chemoresistance after treatment with cisplatin. The results obtained allow us to hypothesize that HIPK2 dysfunction may play a role in fibroblasts behavior and in IPF pathogenesis. HIPK2 may be considered as a novel potential target for anti-fibrosis therapy. J. Cell. Physiol. 228: 235-241, 2013. © 2012 Wiley Periodicals, Inc.Journal of Cellular Physiology 06/2012; 228(1):235-41. · 3.87 Impact Factor -
Article: Reliability of direct sequencing of EGFR: comparison between cytological and histological samples from the same patient.
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ABSTRACT: The results of a recent study have shown the superiority of treatment with gefitinib or erlotinib in lung tumors positive for epidermal growth factor receptor (EGFR) mutation. As a consequence, the complete diagnosis of lung cancer cannot be limited to histotype classification, but should include a series of molecular biology analyses. In most cases, the diagnosis of lung cancer is performed on cytological specimens; therefore, there is a need to obtain a complete and reliable molecular diagnosis on cytologic specimens. Brushing, transbronchial needle aspiration (TBNA) and broncho alveolar lavage during fibro-bronchoscopy allow the sampling of the lung and the mediastinal lymph node. The aim of this study was to demonstrate that direct sequencing of exons 19 and 21 of EGFR in lung tumors, carried out on the cytological samples obtained through fibro-bronchoscopy, is as reliable as the same analysis carried out on a histological surgical sample obtained from the same individual. We considered 50 patients with a histological diagnosis of lung adenocarcinoma whose cytological samples, obtained by fibro-bronchoscopy and histological samples, obtained by surgical resection were available. A comparison of the sensitivity and reliability of the molecular biology analyses carried out on histological and cytological samples of the same patient was carried out. The combined mutation percentage of exons 19 and 21 of EGFR was 10%. The results of the analyses carried out on cytological samples matched those obtained from the histological samples. The feasibility of EGFR analysis on cytological samples has already been demonstrated in previous studies, however these studies referred to the method of fluorescence in situ hybridization, or did not perform any comparison between histological samples from the same patient; our work, on the other hand, shows that direct sequencing of exons 19 and 21 of the EGFR gene is feasible on fibro-bronchoscopy cytological samples with the same reliability offered by the histological samples obtained from the same patient.Anticancer research 12/2011; 31(12):4207-10. · 1.73 Impact Factor
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2012
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Sapienza University of Rome
- Department of Clinical and Molecular Medicine
Roma, Latium, Italy
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