(HPE; 2007-2010); Principal Investigator for IVN Adriana Plesa, PhD
Aim: Finding a way to raise awareness of existing means used in early detection and prevention of cervical cancer
Partners: Coordinator: “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania, Bucur Hospital. – project director Dr. Stanescu Anca Daniela
Partner 1- Institute of Virology Stefan S. Nicolau – responsible Dr. Adriana Plesa
Partner 2– National Institute of Pathology Victor Babeş – responsible Dr. Andrei Florin
Funding: 600 000 LEI
Working team: Plesa A, Anton G, Antipa CE, Botezatu A, Goia C, Bleotu C, Dragodan V
Project financed by PC 4.1.3. contract no 41-081
Implementation period: 10.12.2007 – 15.05.2010
Summary: Proving the presence of papillomavirus DNA in the target tissue is not enough to discern between productive or persistent infection, and less so to prove the imminent neoplasia. The virus-host cell interplay is multilayered and thus, the risk averse patient selection just by detecting viral DNA can lead to overdiagnosis. Some of these patient’s immunity will not allow the viral replication to take place and thus, the viral clearance will appear sooner, while others will develop productive infections in a tissue that sustains viral replication. In both cases, the risk for neoplasia is negligible. Stopping the events in an early stage, either through tissue non-permissiveness (how it is believed to be the case of persistent immature metaplasia) or through the incapability of the viral variant to engage the late stage of infection can lead to the apparition of the tumor. We will investigate the presence of HPV E4 protein and the nucleic acids behind it (taking into account the anti-oncogenic effect and that E4 protein activity is a hallmark of differentiation) in HPV positive patients. We will use molecular biology and immunohistochemistry techniques on cytological samples obtained during screening, and the results will be compared with the histological examination of the immunohistochemical treated samples, with focus on immature metaplasia. From high grade lesions, we will isolate and sequence ORF E4, searching for possible structural alterations that might explain the abortive infection. The cytological and histological study will be performed using a new fixing substance (HOPE), famed to preserve proteins and nucleic acids, allowing for a better detection in both fresh samples and paraffin embedded ones.
Results:
1. Iulia Iancu, Anca Stanescu, Anca Botezatu, Irina Huica, Cristina Goia, Elena Popa, Elena Nistor, Gabriela Anton, Adriana Plesa, Cellular and viral markers in human papillomavirus related cervical lesions progression, Proc. Rom. Acad., 19-23, 2009, ISSN: 1454-8267
2. Iulia Iancu, Anca Botezatu, Cristina Goia-Ruşanu, Anca Stănescu, Irina Huică, Elena Nistor, Gabriela Anton, Adriana Pleşa. TGF-beta signalling pathway factors in HPV-induced cervical lesions. Roum Arch Microbiol Immunol. 2010 69(3):113-8
3. Cristina Goia, Anca Botezatu, Demetra Socolov, Iulia. Iancu, Irina Huica, Adriana Plesa, Gabriela Anton, The implication of mtDNA mutations in HPV-induced cervical cancer, 35th FEBS Congress (Molecules of Life), 26 June-1 July 2010, Gothenburg, Sweden, FEBS Journal, 277 (suppl. 1), Abstract book pag. 91-92; ISSN: 1742-4658. IF=3.13
4. Iulia Iancu, Demetra Socolov, Anca Botezatu, Adriana Plesa, Carmen Ungureanu, Cristina Goia, Gabriela Anton, Expression of TGF-beta/Smads signaling in human cervical cancers, 35th FEBS Congress (Molecules of Life), 26 June-1 July 2010, Gothenburg, Sweden, FEBS Journal, 277 (suppl. 1), Abstract book p. 124-125; ISSN: 1742-4658. IF=3.13
5. Iulia Iancu, Anca Stanescu, Cristina Goia, Adriana Plesa, Elena Popa, Elena Nistor, Gabriela Anton, E6/E7 HPV and p16INK4a expression as predictive markers in cervical carcinogenesis, 34th FEBS Congress, Life’s Molecular Interactions, Praga, Republica Ceha, july 2009, Abstract book p.113. IF=3.13
6. Anca Stănescu, Cristina Goia, Elena Popa, Irina Huică, Ileana Nistor, Gabriela Anton, Adriana Plesa – K-ras oncogene expression and viral DNA status in HPV-associated human cervical neoplasia- Cape Town, Africa de Sud, 04 – 09 octombrie, al 19-lea Congres Mondial de Ginecologie şi Obstetrică – FIGO 2009. Abstract în International Journal of Gynecology and Obstetrics 2009, 10752, S503-S729; 687; ISSN 1470-0328. IF=3.43
7. Gabriela Anton, Demetra Socolov, Anca Botezatu, Cristina Goia, Marina Anton, Anca Stanescu, Adriana Pleşa, S Teleman, Human papillomavirus DNA and mRNA- markers for cervical lesions progression, Third International Congress of Molecular Medicine, May 5-8, 2009, Istanbul, Turkey, Abstract publicat în IUBMB Life, 2009, 61, 344, ISSN 1521-6543. IF= 3.5
8. Anca Stănescu, L. Ples, Gabriela Anton, Adriana Pleşa, Elena Popa, Ruxandra Chiriac. E4 HPV16 gene expression and viral DNA status in HPV-associated human cervical neoplasia, 16th International Meeting of the European Society of Gynaecological Oncology-Belgrad, 11-14 Oct.2009. ISSN: 1525-1438. IF= 1.95
9. Adriana Plesa, Cristina Goia, Anca Botezatu, Coralia Bleotu, Demetra Socolov, Gheorghe Peltecu, Florin Cornitescu, Gabriela Anton, Analysis of HPV DNA and p16 expression to predict prognosis in ASCUS, LSIL and HSIL in cervical swabs, 33rd FEBS Congress and 11th IUBMB Conference, Biochemistry of Cell Regulation, Athens, Greece, 28 june- 3 july 2008, FEBS Journal 275 (Suppl. 1) 99-437 (2008), p. 274; ISSN: 1742-4658. IF=3.39
10. Marina Anton, Gabriela Anton, Zorela Sgarbura, D. Iliescu, Coralia Bleotu, Anca Botezatu, Cristina Goia, Adriana Plesa. E6 human papillomavirus type 16 methylation in clinical specimens. 33rd FEBS Congress and 11th IUBMB Conference, Biochemistry of Cell Regulation, Athens, Greece, 28 iunie- 3 iulie 2008, FEBS Journal 275 (Suppl. 1) 99-437 (2008), p. 102. ISSN: 1742-4658. IF=3.39
11. Gabriela Anton, Demetra Socolov, A.C. Anton, Coralia Bleotu, Marina Anton, F. Cornitescu, S. Teleman, D. Iliescu, Anca Botezatu, Cristina Goia, Adriana Plesa, Viral persistence- factor of cervical lesions progression, HPV in Human pathology, Prague, Chech Republic, 1-3 may 2008, abstract in Central European Journal of Public Health, vol. 16 (JHEMI vol. 52), p26, S61, April 2008; ISSN 1210-7778 (Print) IF=1.481
12. Adriana Plesa, Coralia Bleotu, Cristina. Goia, Anca Botezatu, Elena Popa, Elena Nistor, F. Andrei, Gabriela Anton. p63 value in cervical biopsy tissues, HPV in Human pathology, Prague, Chech Republic, 1-3 may 2008, abstract in Central European Journal of Public Health, vol. 16 (JHEMI vol. 52), p39, S62, April 2008. ISSN 1210-7778 (Print) IF=1.481
