PATRÍCIA SEVERINO

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  • Artigo IPEN-doc 20013
    MicroRNA expression profile in head and neck cancer
    2013 - SEVERINO, PATRICIA; BRUGGEMANN, HOLGER; ANDREGHETTO, FLAVIA M.; CAMPS, CARME; KLINGBEIL, MARIA de F.G.; PEREIRA, WELBERT O. de; SOARES, RENATA M.; MOYSES, RAQUEL; WUNSCH FILHO, VICTOR; MATHOR, MONICA B.; NUNES, FABIO D.; RAGOUSSIS, JIANNIS; TAJARA, ELOIZA H.
    Abstract Background: Current evidence implicates aberrant microRNA expression patterns in human malignancies; measurement of microRNA expression may have diagnostic and prognostic applications. Roles for microRNAs in head and neck squamous cell carcinomas (HNSCC) are largely unknown. HNSCC, a smoking-related cancer, is one of the most common malignancies worldwide but reliable diagnostic and prognostic markers have not been discovered so far. Some studies have evaluated the potential use of microRNA as biomarkers with clinical application in HNSCC. Methods: MicroRNA expression profile of oral squamous cell carcinoma samples was determined by means of DNA microarrays. We also performed gain-of-function assays for two differentially expressed microRNA using two squamous cell carcinoma cell lines and normal oral keratinocytes. The effect of the over-expression of these molecules was evaluated by means of global gene expression profiling and cell proliferation assessment. Results: Altered microRNA expression was detected for a total of 72 microRNAs. Among these we found well studied molecules, such as the miR-17-92 cluster, comprising potent oncogenic microRNA, and miR-34, recently found to interact with p53. HOX-cluster embedded miR-196a/b and miR-10b were up- and down-regulated, respectively, in tumor samples. Since validated HOX gene targets for these microRNAs are not consistently deregulated in HNSCC, we performed gain-of-function experiments, in an attempt to outline their possible role. Our results suggest that both molecules interfere in cell proliferation through distinct processes, possibly targeting a small set of genes involved in cell cycle progression. Conclusions: Functional data on miRNAs in HNSCC is still scarce. Our data corroborate current literature and brings new insights into the role of microRNAs in HNSCC. We also show that miR-196a and miR-10b, not previously associated with HNSCC, may play an oncogenic role in this disease through the deregulation of cell proliferation. The study of microRNA alterations in HNSCC is an essential step to the mechanistic understanding of tumor formation and could lead to the discovery of clinically relevant biomarkers.
  • Artigo IPEN-doc 17729
    Evaluation of microRNA expression in head and neck squamous cell carcinoma cell lines and in primary culture of oral keratinocytes
    2011 - ANDREGHETTO, FLAVIA M.; KLINGBEIL, MARIA F.G.; SOARES, RENATA M.; SITNIK, ROBERTA; PINTO JUNIOR, DECIO dos S.; MATHOR, MONICA B.; NUNES, FABIO D.; SEVERINO, PATRICIA
  • Artigo IPEN-doc 19584
    Cytotoxic effects of mistletoe (Viscum album L.) in head and neck squamous cell carcinoma cell lines
    2013 - KLINGBEIL, MARIA F.G.; XAVIER, FLAVIA C.A.; SARDINHA, LUIZ R.; SEVERINO, PATRICIA; MATHOR, MONICA B.; RODRIGUES, RODRIGO V.; PINTO JUNIOR, DECIO S.
    Head and neck squamous cell carcinoma is a complex disease with several etiologic factors and different molecular changes that may trigger certain events; it is also globally one of the most common malignancies in this topography. Extracts from Viscum album L. (VA) (mistletoe) have been used as adjuvant therapies with promising results in several types of cancer, mainly in European countries. In vitro studies have demonstrated that various types of VA may have cytotoxicity in carcinoma cells, activating the apoptotic cascade or leading cells to necrosis. This study aimed to verify the effects of three types of VA extracts (Iscador Qu Spezial, Iscador P and Iscador M) in squamous cell carcinoma of the tongue cell lines SCC9 and SCC25, not previously studied. A concentration of 0.3 mg/ml (IC50) of the drugs induced apoptosis, affecting gene expression and protein levels of AKT, PTEN and CYCLIN D1. It was concluded that VA extracts have a cytotoxic effect on SCC9 and SCC25 cell lines, but while SCC9 cell line was more resistant to the action of the drugs, Iscador Qu Spezial and Iscador M have higher cytotoxic potential in both cell lines compared to Iscador P.