Damalas A.,University of Ioannina |
Velimezi G.,Molecular Carcinogenesis Group |
Kalaitzakis A.,University of Ioannina |
Liontos M.,Molecular Carcinogenesis Group |
And 3 more authors.
International Journal of Cancer | Year: 2011
The p14 ARF is a key tumor suppressor induced mainly by oncogenic stimuli. Although p14 ARF does not seem to respond to DNA damage, there are very few data regarding its role in other forms of stress, such as heat shock (HS) and oxidative stress (OS). Here, we report that suppression of p14 ARF increased resistance to cell death when cells were treated with H 2O 2 or subjected to HS. In this setting, protection from cell death was mediated by elevated levels and activity of β-catenin, as downregulation of β-catenin alleviated the protective role of p14 ARF silencing. Moreover, Hsp70 was shown to regulate β-catenin protein levels by interacting with p14 ARF, suggesting that Hsp70, p14 ARF and β-catenin form a regulatory network. This novel pathway triggers cell death signals when cells are exposed to HS and OS. © 2010 UICC.
Petrakis T.G.,Molecular Carcinogenesis Group |
Vougas K.,Biomedical Research Foundation of the Academy of Athens |
Gorgoulis V.G.,Molecular Carcinogenesis Group
Transcription | Year: 2012
Research in the last decade revealed an additional role for the Replication Licensing Factor Cdc6 in transcriptional regulation. This novel function has been linked to human cancer development. Here, we summarize all the findings arguing over a role of Cdc6 as a transcriptional repressor and shed light toward new research directions for this field. © 2012 Landes Bioscience.
Nikolaev S.I.,University of Geneva |
Sotiriou S.K.,University of Geneva |
Pateras I.S.,Molecular Carcinogenesis Group |
Santoni F.,University of Geneva |
And 11 more authors.
Cancer Research | Year: 2012
Oncogene-induced DNA replication stress is thought to drive genomic instability in cancer. In particular, replication stress can explain the high prevalence of focal genomic deletions mapping within very large genes in human tumors. However, the origin of single-nucleotide substitutions (SNS) in nonfamilial cancers is strongly debated. Some argue that cancers have a mutator phenotype, whereas others argue that the normal DNA replication error rates are sufficient to explain the number of observed SNSs. Here, we sequenced the exomes of 24, mostly precancerous, colon polyps. Analysis of the sequences revealed mutations in the APC, CTNNB1, and BRAF genes as the presumptive cancer-initiating events and many passenger SNSs. We used the number of SNSs in the various lesions to calculate mutation rates for normal colon and adenomas and found that colon adenomas exhibit a mutator phenotype. Interestingly, the SNSs in the adenomas mapped more often than expected within very large genes, where focal deletions in response to DNA replication stress also map. We propose that single-stranded DNA generated in response to oncogene-induced replication stress compromises the repair of deaminated cytosines and other damaged bases, leading to the observed SNS mutator phenotype. ©2012 American Association for Cancer Research.
Voegele C.,International Agency for Research on Cancer IARC |
Alteyrac L.,Information Technology Services |
Caboux E.,Laboratory Services and Biobank Group |
Smans M.,Information Technology Services |
And 3 more authors.
Bioinformatics | Year: 2010
Summary: Establishment of large-scale biobanks of human specimens is essential to conduct molecular pathological or epidemiological studies. This requires automation of procedures for specimen cataloguing and tracking through complex analytical processes. The International Agency for Research on Cancer (IARC) develops a large portfolio of studies broadly aimed at cancer prevention and including cohort, case-control and case-only studies in various parts of the world. This diversity of study designs, structure, annotations and specimen collections is extremely difficult to accommodate into a single sample management system (SMS). Current commercial or academic SMS are often restricted to a few sample types and tailored to a limited number of analytic workflows [Voegele et al. (2007) A laboratory information management system (LIMS) for a high throughput genetic platform aimed at candidate gene mutation screening. Bioinformatics, 23, 2504-2506].Thus, we developed a system based on a three-tier architecture and relying on an Oracle database and an Oracle Forms web application. Data are imported through forms or csv files, and information retrieval is enabled via multi-criteria queries that can generate different types of reports including tables, Excel files, trees, pictures and graphs. The system is easy to install, flexible, expandable and implemented with a high degree of data security and confidentiality. Both the database and the interface have been modeled to be compatible with and adaptable to almost all types of biobanks. © The Author 2010. Published by Oxford University Press. All rights reserved.
Logotheti S.,National Hellenic Research Foundation |
Michalopoulos I.,Academy of Athens |
Sideridou M.,University of Liverpool |
Daskalos A.,University of Liverpool |
And 7 more authors.
FEBS Journal | Year: 2010
The p73 gene possesses an extrinsic P1 promoter and an intrinsic P2 promoter, resulting in TAp73 and δNp73 isoforms, respectively. The ultimate effect of p73 in oncogenesis is thought to depend on the apoptotic TA to antiapoptotic δN isoforms' ratio. This study was aimed at identifying novel transcription factors that affect TA isoform synthesis. With the use of bioinformatics tools, in vitro binding assays, and chromatin immunoprecipitation analysis, a region extending -233 to -204 bp upstream of the transcription start site of the human p73 P1 promoter, containing conserved Sp1-binding sites, was characterized. Treatment of cells with Sp1 RNAi and Sp1 inhibitor functionally suppress TAp73 expression, indicating positive regulation of P1 by the Sp1 protein. Notably Sp1 inhibition or knockdown also reduces δNp73 protein levels. Therefore, Sp1 directly regulates TAp73 transcription and affects δNp73 levels in lung cancer. TAp73γ was shown to be the only TA isoform overexpressed in several lung cancer cell lines and in 26 non-small cell lung cancers, consistent with Sp1 overexpression, thereby questioning the apoptotic role of this specific p73 isoform in lung cancer. © 2010 FEBS.
Georgakopoulou E.A.,Molecular Carcinogenesis Group |
Scully C.,University College London
Oral Diseases | Year: 2014
Systemic non-biological agents (NBAs) have been extensively used for immunosuppression in clinical medicine, often with considerable efficacy, although sometimes accompanied with adverse effects as with all medicines. With the advent of biological agents, all of which currently are restricted to systemic use, there is a rising need to identify which agents have the better therapeutic ratio. The NBAs include a range of agents, most especially the corticosteroids (corticosteroids). This article reviews the purine synthesis inhibitors (azathioprine and mycophenolate), which are currently the most commonly used systemically immunosuppressive agents in the management of orofacial mucocutaneous diseases. Subsequent articles discuss other corticosteroid-sparing agents used in the management of orofacial disease, such as calcineurin inhibitors, and the cytotoxic and other immunomodulatory agents. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PubMed | Molecular Carcinogenesis Group
Type: Journal Article | Journal: Oral diseases | Year: 2014
Systemic non-biological agents (NBAs) have been extensively used for immunosuppression in clinical medicine, often with considerable efficacy, although sometimes accompanied with adverse effects as with all medicines. With the advent of biological agents, all of which currently are restricted to systemic use, there is a rising need to identify which agents have the better therapeutic ratio. The NBAs include a range of agents, most especially the corticosteroids (corticosteroids). This article reviews the purine synthesis inhibitors (azathioprine and mycophenolate), which are currently the most commonly used systemically immunosuppressive agents in the management of orofacial mucocutaneous diseases. Subsequent articles discuss other corticosteroid-sparing agents used in the management of orofacial disease, such as calcineurin inhibitors, and the cytotoxic and other immunomodulatory agents.