Gerassimos E Voutsinas

Institute of Biosciences and Applications 
NCSR "Demokritos" 
15310 Athens 
Greece 
tel: +30.210.6503579 
fax: +30.210.6511767

mvoutsin@bio.demokritos.gr

CURRICULUM VITAE

Gerassimos VOUTSINAS
Principal Investigator
Lab of Environmental Mutagenesis and Carcinogenesis
Institute of Biosciences and Applications
National Center for Scientific Research “Demokritos”
Patriarchou Grigoriou and Neapoleos str.
15310 Aghia Paraskevi Attikis, Greece
Tel: (+30 210) 650 3579, 650 3622
Fax: (+30 210) 651 1767
email: mvoutsin@bio.demokritos.gr
Home address: 74, El. Venizelou str., 15561 Holargos, Athens, Greece
Tel: (+30) 2130261751
Mob: (+30) 6976228332
List of publications online at: http://publicationslist.org/g.e.voutsinas

I. PERSONAL DATA
Date and place of birth: January 10, 1958, Piraeus, Greece
Nationality: Greek
Family status: Married, one daughter
Language skills: English, French

II. EDUCATION AND PROFESSIONAL APPOINTMENTS
1983: B.Sc., Dept. of Biology, Aristotle University of Thessaloniki, Greece.
1983-87: Ph.D. student, Institute of Biology, NCSR "Demokritos", Athens, Greece
1987-88: Research associate, Lab. of Environmental Mutagenesis and Carcinogenesis, Institute of Biology, NCSR "Demokritos", Athens, Greece, European Union (EU) Project “Genetic effects of environmental chemicals”
1988-91: Research associate, Lab. of Environmental Mutagenesis and Carcinogenesis, Institute of Biology, NCSR "Demokritos", Athens, Greece, EU Project “Mechanisms of induced non-disjunction and validation of tests for genomic mutations”
1991-94: Research associate, Lab. of Environmental Mutagenesis and Carcinogenesis, Institute of Biology, NCSR "Demokritos", Athens, Greece, EU Project “The detection and evaluation of aneugenic chemicals”
1993: Ph.D., Dept. of Biology, University of Patras, Greece: “Comparative study on the mutagenic activity of new anticancer alkylating agents in Salmonella typhymurium and Aspergillus nidulans”
1994-96: Research associate, Lab. of Molecular Oncology, Dept. of Medical Genetics, Faculty of Medical Sciences, University of Groningen, The Netherlands, EU Project “Regulation of a gene with similarity to the gene for ubiquitin-activating enzyme and with greatly reduced expression in lung cancer”
1996-99: Research associate, Lab. of General Biology, School of Medicine, University of Patras, Greece, Greek General Secretariat of Research and Technology Project “Development of new biotechnological approaches for the diagnosis, prevention and therapy of inherited and acquired diseases of the Greek entity”
1997 European Collection of Animal Cell Cultures, Centre of Applied Microbiology and Research, Salisburry, UK, “Immortalization of B lymhocytes with the help of Epstein-Barr virus”
1999-2009: Staff research scientist (grade C), Lab. of Environmental Mutagenesis and Carcinogenesis, Institute of Biology, NCSR "Demokritos", Athens, Greece
2009-to date: Principal Investigator (grade B), (1) Lab. of Environmental Mutagenesis and Carcinogenesis, Institute of Biosciences and Applications, NCSR "Demokritos", (2) Lab. of Molecular Diagnosis of Genetic Diseases, Athens, Greece

III. TEACHING EXPERIENCE
1. Lecturer of the undergraduate course “Introduction to Molecular Biology” at the American College of Greece (2007-present day)
2. Lecturer of the undergraduate course “Environmental Health” at the American College of Greece (2013)
3. Lecturer of the post-graduate course "An Introduction to Cancer Genetics" at the Institute of Biology, NCSR "Demokritos" (1999-2008)
4. Lecturer of the post-graduate course “Principles in cancer chemotherapy” (seminar and practical exercise) (2006-2012), “Pharmacological targeting of Hsp90 in human cancers” (2010-2012), and “Molecular diagnosis of genetic diseases” (2010-2013) at the National and Kapodistrian University of Athens
5. Lecturer of the post-graduate courses “The production of mutations: endogenous and environmental factors”, “Mutation detection techniques” and “The molecular pathogenesis of cancer” at the Medical School of the University of Patras (1999-2004)
6. Lecturer at the summer schools of NCSR "Demokritos" (1999-2006)
7. High-school teacher (1997-1999)

IV. HONORS
• 3 fellowships (Greek Atomic Energy Commission, European Union, British Council)
• 4 awards for research studies presented in scientific meetings

V. INVITED SPEAKER
• In 16 scientific meetings

VI. ORGANIZING COMMITTEE MEMBER
• In 9 scientific meetings

VII. REVIEWER
A. Articles in International Scientific Journals
1. International Journal of Cancer
2. Molecular and Cellular Biochemistry
3. Tumor Biology
4. Chemotherapy Journal
5. PLoS ONE
6. Nature Reviews Urology

B. Fellowships
1. International Cancer Research Technology Transfer (ICRETT) Fellowships awarded by the Union for International Cancer Control.
2. Yamagiwa-Yoshida Memorial International Study (YY) Grants awarded by the Union for International Cancer Control.

VIII. OTHER ACTIVITIES
1. Supervisor of the Laboratory of Molecular Diagnosis of Genetic Diseases (E1609), NCSR “Demokritos”, providing the appropriate service
2. Responsible for the ΑΒΙ Prism 310 Genetic Analyzer (Applied Biosystems), the Mx3000P QPCR System (Stratagene), the Image Analysis System (Vilber Lourmat), the LAS-4000 Luminescent Image Analyzer (Fuji-Film) and the FLA-7000 Fluorescent Image Analyzing System (Fuji-Film) of the Institute of Biosciences and Applications, NCSR "Demokritos"
3. Committee member at the IBA, NCSR “Demokritos”: 11 Supervisory committees for PhD students, eight (8) examination committees for new PhD students, six (6) committees for hiring new research associates
4. Supervisory committee member at Greek Universities: 11 committees for master degree, 4 PhD committees, at the National and Kapodistrian University of Athens, Greece
5. Supervisor of 2 post-doctoral fellows, 1 UICC fellow, 11 post-graduate students, 7 associate post-graduate students, 7 undergraduate students, 11 summer students, 14 rotating PhD students and 1 technician of the Institute of Biosciences and Applications, NCSR "Demokritos"
6. Member of the Hellenic Society of Biological Sciences, the Hellenic Society of Biochemistry and Molecular Biology, the Association of Medical Geneticists of Greece, the Hellenic Association for Molecular Cancer Research and the Pan-hellenic Union of Bioscientists.
7. Member of the Scientific Committees of Tuberous Sclerosis Association of Greece (2001-present day) and Greek Alliance for Rare Diseases (2003-present day)
8. Member of the Board of Directors of the Greek Alliance for Rare Diseases (2003-present day)
9. Member of the NATO pilot study program: "Pilot Study on Advanced Risk Assessment Methods" (1999-2005)
10. Author of 2 articles in the Greek daily press
11. Author of 14 popularized scientific articles in the daily and periodical Greek press

IX. CURRENT RESEARCH INTERESTS
1. Identification and validation of drug targets for cancer therapy
2. Development and evaluation of biomarkers for diagnosis, prognosis and treatment response in human disease
3. Development of genetic testing protocols for molecular diagnosis of human genetic diseases

X. EXTRAMURAL FUNDING
Research project: Regulation of apoptosis inhibition and development of resistance to chemotherapy by geldanamycin: a new chemotherapeutic drug with a specific molecular target.
Funded by the Greek Ministry for Health and Social Solidarity.
Project Leader: G.E. Voutsinas
Duration from-to: 1/1/2006 – 31/12/2007
Total funding: 14,650 €.

Research project: TSC1 and TSC2 genetic alterations in Tuberous Sclerosis.
Funded by the Greek General Secretariat for Research and Technology.
Project Leader: G.E. Voutsinas
Duration from-to: 1/4/2006 – 31/3/2008
Total funding: 11,740 €.

Research project: Development of a pharmacogenomic platform as a reliable molecular tool against human urinary bladder cancer.
Funded by the Hellenic Society of Medical Oncology.
Project Leader: G.E. Voutsinas
Duration from-to: 1/11/2007 – 31/10/2008
Total funding: 6,000 €.

Research project: Structural and functional analysis of genes involved in the PI3K signal transduction pathway in urinary bladder cancer: effects on prognosis and therapy. Funded by the Greek Ministry of Health and Social Solidarity.
Project Leader: G.E. Voutsinas
Duration: 1/9/2008 – 31/8/2010
Total funding: 12,000 €.

Research project: Decoding of the apoptotic potential of the specific inhibitor of proteasome activity Bortezomib (Velcade) in targeted chemotherapy of human urinary bladder cancer.
Funded by the Hellenic Society of Medical Oncology.
Project Leader: D.J. Stravopodis (Dept of Biology, University of Athens, Greece)
Duration: 1/12/2009 – 31/11/2010
Total funding: 5,000 €.

Research project: Inhibition of Hsp90 as a new therapeutic tool against human urinary bladder cancer.
Funded by the Empeirikos Foundation.
Project Leader: D.J. Stravopodis (Dept of Biology, University of Athens, Greece)
Duration: 1/7/2010 – 30/6/2011
Total funding: 12,000 €.

Research project: Molecular diagnosis of Neurofibromatosis type 1.
Funded by the American College of Greece.
Project Leader: G.E. Voutsinas
Duration: 1/11/2010 – 31/10/2011
Total Funding: 10,000 €.

XI. PUBLICATIONS AND RELATED INFORMATION
• 41 peer-reviewed articles in International Scientific Journals
• 4 peer-reviewed book chapters
• 1 non-peer-reviewed article in a Greek Journal (in English)
• 86 abstracts in International Journals and Congress Proceedings
• Impact Factor (total): 133,887
• Impact Factor (mean): 3,265
• Total number of citations: 560
• Self-citations of all authors excluded: 493
• h-factor: 13

XII. PEER-REVIEWED ARTICLES
1. Voutsinas, G., A. Kappas, N.A. Demopoulos and P. Catsoulacos (1993) Comparative study on the mutagenicity of three structurally related substituted aniline mustards in the Salmonella/microsome assay, Mutation Res. 298, 261-267. (IF: 2.188)
2. Voutsinas, G., A. Kappas, N.A. Demopoulos, and P. Catsoulacos (1993) Mutagenic activity of the antitumour agent homo-aza-steroidal ester of p-N,N-bis(2-chloroethyl)amino-phenoxyacetic acid (NSC 294859) in the Salmonella/microsome assay, Mutagenesis 8, 431-435. (IF: 2.094)
3. Voutsinas, G., A. Kappas, N.A. Demopoulos, and C. Camoutsis (1993) Mutagenicity of four homo-aza-steroidal esters of m-N,N-bis(2-chloroethyl)aminocinnamic acid in the Ames test, Mutation Res. 319, 325-329. (IF: 2.188)
4. Gichner, T., G. Voutsinas, A. Patrineli, A. Kappas and M.J. Plewa (1994) Antimutagenicity of three isomers of aminobenzoic acid in Salmonella typhimurium, Mutation Res. 309, 201-210. (IF: 3.340)
5. Parry, J.M., E.M. Parry, R. Bourner, …, A. Kappas, G. Voutsinas, F.E. Zarani, A. Patrinelli, F. Pacchierotti, C. Tiveron and P. Hess (1996) The detection and evaluation of aneugenic chemicals, Mutation Res. 353, 11-46. (IF: 3.340)
6. Voutsinas, G., F.E. Zarani and A. Kappas (1997) The effect of environmental aneuploidy-inducing agents on the microtubule architecture of mitotic meristematic root cells in Hordeum vulgare, Cell Biology International 21, 411-418. (IF: 1.194)
7. Vachkova, R., A. Kappas, E. Tyagunenko, M. Markaki and G. Voutsinas (1998) Specific recombinogenic activity of a new polyene antibiotic, Cellular and Molecular Life Sciences 54, 143-147. (IF: 4.582)
8. Timmer, T., P. Terpstra, A. van den Berg, P.M.J.F. Veldhuis, A. ter Elst, G. Voutsinas, M.M.F. Hulsbeek, T.G. Draaijers, M. Looman, K. Kok, S.L. Naylor and C.H.C.M. Buys (1999) A comparison of genomic structures and expression patterns of two closely related flanking genes in a critical lung cancer region at 3p21.3, Eur J Hum Genet 7, 478-486. (IF: 3.251)
9. Athanassiadou, A., G. Voutsinas, L. Psiouri, E. Leroy, M.H. Polymeropoulos, A. Ilias, G.M. Maniatis and T. Papapetropoulos (1999) Genetic analysis of Parkinson’s Disease families carrying the Ala53Thr mutation in the gene encoding α-synuclein, American Journal of Human Genetics 65, 555-558. (IF: 12.649)
10. Voutsinas G. (2001) Mutagenesis, apoptosis, basic relation to carcinogenic models, Folia Histochemica et Cytobiologica 39 suppl 2, 56-57. (IF: 0.789)
11. Michalopoulos, N.V., A. Saetta, A.Ch. Lazaris, G. Voutsinas and P.S. Davaris (2003) Detection of genetic abnormalities in neoplasms from Greek patients with FAP, European Journal of Surgical Oncology 29, 38-43. (IF: 3.184)
12. Puiu L., E. Petrakou, A. Apostolidou, A. Athanassiadou, L. Psiouri, A. Papachatzopoulou, V.G. Gorgoulis, A. Kotsinas, E. Tzoracoeleftherakis, G.M. Maniatis and G. Voutsinas (2003) Lack of Fas (APO-1/CD95) gene structural alterations or transcript variant ratio changes in breast cancer, Cancer Letters 194, 91-97. (IF: 3.049)
13. Korkolopoulou, P., A. Goudopoulou, G. Voutsinas, E. Thomas-Tsagli, E. Patsouris and A. Saetta (2004) FLIP expression in bladder urothelial carcinomas: its role in resistance to Fas-mediated apoptosis and clinicopathological correlations, Urology 63, 1198-1204. (IF: 2.139)
14. Sevinç, A., D. Yannoukakos, I. Konstantopoulou, E. Manguoglu, G. Lüleci, T. Çolak, C. Akyerli, G. Çolakoglu, M. Tez, I. Sayek, G. Voutsinas, G. Nasioulas, E. Papadopoulou, L. Florentin, E. Kontogianni, B. Bozkurt, N.A. Kocabaş, A.E. Karakaya, I.G. Yulug and T. Özçelik (2004) No association between RNASEL Arg462Gln variant and breast cancer risk, Anticancer Research 24, 2547-2549. (IF: 1.604)
15. Saetta, A.A., A. Goudopoulou, P. Korkolopoulou, G. Voutsinas, E. Thomas-Tsagli, N.V. Michalopoulos and E. Patsouris (2004) Mononucleotide markers of microsatellite instability in carcinomas of the urinary bladder, European Journal of Surgical Oncology 30, 796-803. (IF: 3.184)
16. Bakas, P.G., A.E. Liapis, I. Zervolea, G. Voutsinas, D. Kletsas and G. Creatsas (2004) mRNA assessment for procollagen production in women with genuine stress urinary incontinence, International Urogynecological Journal of Pelvic Floor Dysfunctions 15, 429-431. (IF: 1.907)
17. Poulaki, V., C.S. Mitsiades, C. McMullan, G. Fanourakis, J. Negri, A. Goudopoulou, I.X. Halikias, G. Voutsinas, S. Tseleni-Balafouta, J.W. Miller and N. Mitsiades (2005) Human retinoblastoma cells are resistant to apoptosis induced by death receptors: Role of caspase-8 gene silencing, Investigative Ophthalmology and Visual Science 46, 358-366. (IF: 3.643)
18. Tseleni-Balafouta, S., H. Gakiopoulou, G. Fanourakis, G. Voutsinas, D. Balafoutas and E. Patsouris (2006) Tenascin-C protein expression and mRNA splice variants in thyroid carcinoma, Experimental and Molecular Pathology 80, 177-182. (IF: 2.089)
19. Tseleni-Balafouta, S., H. Gakiopoulou, G. Fanourakis, G. Voutsinas, H. Litsiou, E. Sozopoulos, D. Balafoutas and E. Patsouris (2006) Fibrillin expression and localization in various types of carcinomas of the thyroid gland, Modern Pathology 19, 695-700. (IF: 3.426)
20. Mitsiades, C.S., V. Poulaki, G. Fanourakis, E. Sozopoulos, D. McMillin, Z. Wen, G. Voutsinas, S. Tseleni-Balafouta and N. Mitsiades (2006) Fas signaling in thyroid carcinomas is diverted from apoptosis to proliferation, Clinical Cancer Research 12, 3705-3712. (IF: 5.715)
21. Mitsiades, C.S., V. Kotoula, V. Poulaki, E. Sozopoulos, J. Negri, E. Charalambous, G. Fanourakis, G. Voutsinas, S. Tseleni-Balafouta and N. Mitsiades (2006) EGFR as a therapeutic target in human thyroid carcinoma: mutational and functional analysis, Journal of Clinical Endocrinology and Metabolism 91, 3662-3666. (IF: 6.020)
22. Mitsiades, C.S., J. Negri, C. McMullan, D.W. McMillin, E. Sozopoulos, G. Fanourakis, G. Voutsinas, S. Tseleni-Balafouta, V. Poulaki, D. Batt and N. Mitsiades (2007) Targeting BRAFV600E in thyroid carcinoma: therapeutic implications, Molecular Cancer Therapeutics 6, 1070-1078. (IF: 5.171)
23. Stavropoulou, C., D. Korakaki, H. Rigana, G. Voutsinas, M. Polyzoi, V. Georgakakos, K. Manola, C. Karageorgiou and C. Sambani (2007) Glutathione S-transferase T1 and M1 gene polymorphisms in Greek patients with multiple sclerosis: a pilot study, European Journal of Neurology 14, 572-574. (IF: 2.244)
24. Stravopodis, D.J., L.H. Margaritis and G.E. Voutsinas (2007) Drug-mediated targeted disruption of multiple protein activities through functional inhibition of the Hsp90 chaperone complex, Current Medicinal Chemistry 14, 3122-3138. (IF: 5.207)
25. Stavropoulou, C., C. Sambani, H. Rigana, V.N. Georgakakos, G. Voutsinas, K.N. Manola, G.E. Pantelias and V. Makropoulos (2008) Low frequency of the glutathione-S-transferase T1-null genotype in patients with primary myelodysplastic syndrome and 5q deletion, Leukemia 22, 1643-1646. (IF: 6.146)
26. Lampidonis, A.D., A. Argyrokastritis, D.J. Stravopodis, G.E. Voutsinas, T.G. Ntouroupi, L.H. Margaritis, I. Bizelis and E. Rogdakis (2008) Cloning and functional characterization of the ovine Hormone Sensitive Lipase (HSL) full-length cDNAs: an integrated approach, Gene 416, 30-43. (IF: 2.721)
27. Stravopodis, D.J., A.Z. Zapheiropoulos, G.E. Voutsinas, L.H. Margaritis and I.S. Papassideri (2008) A PCR-based integrated protocol for the structural analysis of the 13th exon of the human beta-myosin heavy chain gene (MYH7): Development of a diagnostic tool for HCM disease, Exp Mol Pathol 84, 245-250. (IF: 1.377)
28. Gioni, V., T. Karabinas, G. Voutsinas, A.E. Roussidis, S. Papadopoulos, N.K. Karamanos and D. Kletsas (2008) Imatinib mesylate inhibits the proliferation and collagen synthesis in human breast stromal fibroblasts, Molecular Cancer Research 6, 706-714. (IF: 4.759)
29. Lampidonis, A.D., D.J. Stravopodis, G.E. Voutsinas, N. Messini-Nikolaki, G.C. Stefos, L.H. Margaritis, A. Argyrokastritis, I. Bizelis and E. Rogdakis (2008) Structural characterization and functional analysis of the promoter region of Hormone-Sensitive Lipase (HSL) gene of the sheep (Ovis aries), Gene 427, 65-79. (IF: 2.721)
30. Stravopodis, D.J., P.K. Karkoulis, E.G. Konstantakou, S. Melachroinou, D. Anastasiou, S. Kachrilas, A.D. Lampidonis, N. Messini-Nikolaki, I.S. Papassideri, G. Aravantinos, L.H. Margaritis and G.E. Voutsinas (2009) Grade-dependent regulation of cell cycle progression and apoptosis in response to doxorubicin in human bladder cancer cell lines, Int J Oncol 34, 137-160. (IF: 2.556)
31. Kotoula, V., E. Sozopoulos, H. Litsiou, G. Fanourakis, T. Koletsa, G. Voutsinas, S. Tseleni-Balafouta, C.S. Mitsiades, A. Wellmann and N. Mitsiades (2009) Mutational analysis of the BRAF, RAS and EGFR genes in human adrenocortical carcinomas, Endocrine-Related Cancer, 16, 565-572. (IF: 4.763)
32. Konstantakou, E.G., G.E. Voutsinas, P.K. Karkoulis, G. Aravantinos, L.H. Margaritis, and D.J. Stravopodis (2009) Human bladder cancer cells undergo cisplatin-induced apoptosis that is associated with p53-dependent and p53-independent responses, Int J Oncol 35, 401-416. (IF: 2.556).
33. Voutsinas, G.E. and D.J. Stravopodis (2009) Molecular targeting and gene delivery in bladder cancer therapy, J BUON 14 (suppl 1), S69-S78. (IF=-)
34. Sozopoulos E., H. Litsiou, G. Voutsinas, N. Mitsiades, N. Anagnostakis, T. Tseva, E. Patsouris and S. Tseleni-Balafouta (2010) Mutational and immunohistochemical study of the PI3K/Akt pathway in papillary thyroid carcinoma in Greece, Endocr Pathol 21, 90-100. (IF=1.417)
35. Voutsinas G.E., E.F. Stavrou, G. Karousos, A. Dasoula, A. Papachatzopoulou, M. Syrrou, A.J.M.H. Verkerk, P. van der Spek, G.P. Patrinos, R. Stöger and A. Athanassiadou (2010) Allelic imbalance of expression and epigenetic regulation within the alpha-synuclein wild-type and p.Ala53Thr alleles in Parkinson disease, Hum Mutat 31, 685-691. (IF=6.887)
36. Karkoulis, P.K., D.J. Stravopodis, L.H. Margaritis and G.E. Voutsinas (2010) 17-Allylamino-17-demethoxygeldanamycin induces downregulation of critical Hsp90 protein clients and results in cell cycle arrest and apoptosis of human urinary bladder cancer cells, BMC Cancer 10:481. (IF=2.74)
37. Stravopodis, D.J., P.K. Karkoulis, E.G. Konstantakou, S. Melachroinou, A. Thanasopoulou, G. Aravantinos, L.H. Margaritis, E. Anastasiadou and G.E. Voutsinas (2011) Thymidilate synthase inhibition induces p53-dependent and p53-independent apoptotic responses in human urinary bladder cancer cell lines, J Cancer Res Clin Oncol 137, 359-374. (IF=2.261)
38. Lampidonis, A.D., E. Rogdakis, G.E. Voutsinas and D.J. Stravopodis (2011) The resurgence of Hormone-Sensitive Lipase (HSL) in mammalian lipolysis, Gene 477, 1-11. (IF=2.721)
39. Pliarchopoulou, K., G. Voutsinas, G. Papaxoinis, K. Florou, M. Skondra, K. Kostaki, P. Roussou, K. Syrigos and D. Pectasides (2012) Correlation of CYP1A1, GSTP1 and GSTM1 gene polymorphisms and lung cancer risk among smokers, Oncol Lett 3, 1301-1306. (IF=0.108)
40. Karkoulis, P.K., D.J. Stravopodis, E.G. Konstantakou and G.E. Voutsinas (2013) Targeted inhibition of heat shock protein 90 disrupts multiple oncogenic signaling pathways, thus inducing cell cycle arrest and programmed cell death in human urinary bladder cancer cell lines, Cancer Cell International 13, 11. (IF=1.973)
41. Stavropoulou, A.V., F. Fostira, M. Pertesi, M. Tsitlaidou, G.E. Voutsinas, O. Triantafyllidou, A. Bamias, M.A. Dimopoulos, E. Timotheadou, D. Pectasides, C. Christodoulou, G. Klouvas, C. Papadimitriou, T. Makatsoris, G. Pentheroudakis, G. Aravantinos, V. Karydakis, D. Yannoukakos, G. Fountzilas, I. Konstantopoulou (2013) Prevalence of BRCA1 Mutations in Familial and Sporadic Greek Ovarian Cancer Cases, PLOS ONE 8, e58182. (IF=4.092)

XIII. PEER-REVIEWED BOOK CHAPTERS
1. Cogliano, V.J., A. Kappas, G. Voutsinas and G.A. Zapponi (1999) The biological basis of cancer, in: V.J. Cogliano, E.G. Luebeck and G.A. Zapponi (eds) Perspectives on Biologically Based Cancer Risk Assessment, Plenum, New York, pp 21-47.
2. McLaughlin, P.M.J., G. Voutsinas, K. Kok, M.G.L. Brinker, R. Vos, P. Terpstra, M.C. Harmsen, M.H.J. Ruiters, L.F.M.H. de Leij and C.H.C.M. Buys (2000) Characterization and analysis of the UBE1L promoter in lung cancer-derived cell lines and in UBE1L promoter-driven green fluorescent protein transgenic mice, in: P.M.J McLaughlin (PhD Thesis) Lung cancer associated genes studied in vitro and in vivo using transgenic animal models, Faculty of Medical Sciences, State University of Groningen, Groningen, Netherlands, pp 117-127.
3. G. Voutsinas (2002) Mutagenesis, Apoptosis, Basic relation to carcinogenic models, in: L. Chyczewski, J. Niklinski and E. Pluygers (eds) Endocrine Disrupters and Carcinogenic Risk Assessment, IOS Press, Amsterdam, pp 338-346.
4. Voutsinas, G., A. Apostolidou and N. Spyrou (2005) New data from molecular cancer epidemiology, in: L. Edler and C. Kitsos (eds), Quantitative Methods in Cancer and Human Health Risk Assessment, John Wiley and Sons, Chichester, UK, pp. 29-41.
5. Voutsinas, G., V. Biliou, J. Traeger-Synodinos, D. Synodinos, S. Youroukos, D. Yannoukakos and M. Lambrou (2013) Rare Disease patients: neglected by the health care system, submitted.

XIV. NON-PEER-REVIEWED ARTICLES
1. Voutsinas, G.E., R. Vrtel, E. Anastasiadou and D.J. Stravopodis (2008) Molecular genetic diagnosis of the Tuberous Sclerosis Complex, ΒΙΟ 28, 24-29.

XV. LIST OF ABSTRACTS IN INTERNATIONAL JOURNALS AND CONGRESS PROCEEDINGS
1. Voutsinas, G., and A. Kappas (1987) Adaptive response to the mutagenic action of alkylating agents in the fungus Aspergillus nidulans, Abstracts of the 8th Congress of the Hellenic Society of Biological Sciences, Ioannina, Greece, p. 96-97.
2. Voutsinas, G. and A. Kappas (1987) Adaptive response to the mutagenic action of alkylating agents, Eur. J. Cancer Clin. Onc. 23, 1811.
3. Voutsinas, G. and A. Kappas (1988) On the induced adaptability of Aspergillus nidulans to the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine, Mutation Res. 203, 217-218.
4. Voutsinas, G., A. Kappas, N.A. Demopoulos, and P. Catsoulacos (1989) Genotoxic activity of cytostatic alkylating agents in the Salmonella/microsome assay, Abstracts of the 11th Congress of the Hellenic Society of Biological Sciences, Komotini, Greece, p. 140-142.
5. Voutsinas, G., A. Kappas, N.A. Demopoulos and P. Catsoulacos (1990) Genotoxic activity of three isomers of N,N-bis(2-chloroethyl)aminocinnamic acid in the Salmonella typhimurium/mammalian microsome test, Mutation Res. 234, 407.
6. Voutsinas, G., A. Kappas, N.A. Demopoulos and C. Camoutsis (1990) The effect of different homo-aza-steroidal esters of m-N,N-bis(2-chloroethyl)aminocinnamic acid on mutation induction in the Salmonella typhimurium/mammalian microsome test, Mutation Res. 234, 413-414.
7. Kappas, A., M. Markaki, G. Voutsinas, K. Tsakiri and A. Patrineli (1991) On the validation of test systems for genomic mutations. Effects of various chemicals on mitosis of Aspergillus nidulans, CEC Contact Group Meeting "Genetic Effects of Environmental Chemicals", Estoril, Portugal.
8. Voutsinas, G., F.E. Zarani, and A. Kappas (1992) Effects of aneugenic chemicals on the microtubule structure in Aspergillus nidulans protoplasts, Abstracts of the NATO Advanced Research Workshop on Chromosome Segregation and Aneuploidy, Crete, Greece, p. 74.
9. Kappas, A., G. Voutsinas, and F.E. Zarani (1992) On the mechanisms of chemically-induced aneuploidy in Aspergillus nidulans, CEC Contact Group Meeting "The Detection and Evaluation of Aneugenic Chemicals", Crete, Greece.
10. Kappas, A., G. Voutsinas and A. Patrineli (1992) Inhibition of chemically-induced mutations by various agents, 3rd NATO-CCMS Pilot Study Meeting on Risk Assessment for Initiator and Promoter Carcinogens, Athens, Greece.
11. Voutsinas, G. and A. Kappas (1993) Mutagenicity of a new antitumor agent in Salmonella, Abstracts of the XIIth Meeting of the European Association for Cancer Research, Brussels, Belgium, no 55.
12. Kappas, A., T. Gichner, G. Voutsinas and A. Patrineli (1993) Inhibition of the mutagenic action of N-methyl-N'-nitro-N-nitrosoguanidine by the aminobenzoic acid isomers in Salmonella, Abstracts of the 15th Congress of the Hellenic Society of Biological Sciences, Florina-Kastoria, Greece, p. 61-63.
13. Voutsinas, G., F.E. Zarani and A. Kappas (1993) Cytological study on interphase and mitotic nuclei in Aspergillus nidulans germlings and protoplasts, Abstracts of the 15th Congress of the Hellenic Society of Biological Sciences, Florina-Kastoria, Greece, p. 217-220.
14. Voutsinas, G., F.E. Zarani and A. Kappas (1993) Anti-tubulin indirect immunofluorescence study in benomyl-treated meristematic cells of Hordeum vulgare, CEC Contact Group Meeting "The Detection and Evaluation of Aneugenic Chemicals", Barcelona, Spain.
15. Voutsinas, G., F.E. Zarani and A. Kappas (1993) Interphase and mitotic nuclei in Aspergillus, Abstracts of the Seventeenth International Congress of Genetics, Birmingham, UK, no 30.
16. Kappas, A. and G. Voutsinas (1993) Inhibition in mutagenesis and carcinogenesis, 4th NATO-CCMS Pilot Study Meeting on Risk Assessment for Initiator and Promoter Carcinogens, Lisbon, Portugal.
17. Voutsinas, G. and A. Kappas (1993) Anticancer agents of similar chemical structure show different mutagenic activities, European Journal of Cancer 29A, Suppl. 6, S88.
18. Voutsinas, G., F.E. Zarani and A. Kappas (1994) Effect of aneugenic chemicals on spindle architecture in meristematic root cells of Hordeum vulgare, 3rd CEC Contact Group Meeting "The Detection and Evaluation of Aneugenic Chemicals", Corfu, Greece.
19. Kappas, A. and G. Voutsinas (1994) Health effects of lead and aromatic hydrocarbons from vehicle emissions, Seminar of the British Hellenic Chamber of Commerce in "Urban Air Quality - Environmental and Health Effects of Motor Vehicle Fuel Composition", Athens, Greece.
20. Kappas, A. and G. Voutsinas (1994) Genetic toxicology testing of environmental mutagens and aneugens, Abstracts of the XVIth International Cancer Congress, New Delhi, India.
21. Voutsinas, G., F.E. Zarani and A. Kappas (1994) Effect of the antibiotic griseofulvin in the organization of the mitotic spindle of meristematic cells in the plant Hordeum vulgare, Abstracts of the 16th Congress of the Hellenic Society of Biological Sciences, Volos, Greece.
22. Kappas, A. and G. Voutsinas (1994) The detection of aneugenic chemicals in Aspergillus, Abstracts of the Fifth International Mycological Congress, Vancouver, Canada.
23. Voutsinas, G., F. Zarani and A. Kappas (1995) Griseofulvin-induced disorganization of the spindle in meristematic cells of Hordeum vulgare, An International Conference on "Chromosome Segregation and Aneuploidy, Sorrento, Italy.
24. Voutsinas, G., A. van den Berg and C.H.C.M. Buys (1995) Characterization of the promoter region of the human UBE1L gene, Abstracts of the Annual Meeting of the Dutch Foundation for Medical and Health Research, Genetics Working Groups, Maastricht/ Kerkrade, The Netherlands.
25. Voutsinas, G., A. van den Berg and C.H.C.M. Buys (1996) Identification of regulatory elements in the promoter region of the human UBE1L gene, European Journal of Human Genetics vol. 4, suppl. 1, 64-65.
26. Voutsinas, G., K. Kok, A. van den Berg and C.H.C.M. Buys (1996) Identification of the regulatory region of the human UBE1L gene, which is characterized by a greatly reduced expression in lung cancer, Abstracts of the 18th Congress of the Hellenic Society of Biological Sciences, Kalamata, Greece, p. 66-68.
27. Athanassiadou, A., G. Voutsinas, L. Psiouri, M. Polymeropoulos, A. Elias and T. Papapetropoulos (1998) The occurrence of α-synuclein mutation in families with Parkinson’s Disease, Abstracts of the Annual Hugo Meeting - HGM’98, Turin, Italy, no 11, p. 3.
28. Athanassiadou, A., G. Voutsinas, L. Psiouri, M. Polymeropoulos, A. Elias and T. Papapetropoulos (1998) Genetic analysis of α-synuclein G209A mutation in familial Parkinson’s Disease, Abstracts of the 3rd Balkan Meeting on Human Genetics, Thessaloniki, Greece, no 0.21, p. 55.
29. Athanassiadou, A., G. Voutsinas, L. Psiouri, M. Polymeropoulos, A. Ilias and T. Papapetropoulos (1998) Analysis of familial Parkinson’s Disease associated with alpha-synuclein G209A mutation, American Journal of Human Genetics 63 suppl, A27, 137.
30. Timmer, T., P. Terpstra, A. van den Berg, P.M.J.F. Veldhuis, A. ter Elst, G. Voutsinas, M.M.F. Hulsbeek, T.G. Draaijers, M. Looman, K. Kok, S.L. Naylor and C.H.C.M. Buys (1998) A comparison of two closely related and flanking genes in the critical lung cancer region at 3p21.3 with respect to genomic structure and expression, American Journal of Human Genetics 63 suppl, A89, 488.
31. Voutsinas, G. and A. Kappas (1999) Environmental mixtures: complex patterns of exposure, CCMS/NATO Pilot Study Meeting on Advanced Cancer Risk Assessment Methods, November 13-16, 1999, Rome, Italy.
32. Konstantopoulou I, Ladopoulou A., Pantazidis A, Kotsinas A., Gorgoulis V.G., Kittas C., Tsionou C., Minaretzis D., Voutsinas G., Athanassiadou A., Tzoracoelephtherakis E., Florentin L., Nounesis G., Chiotellis E., Yannoukakos D. and the Greek Consortium for BRCA1 and BRCA2 Mutation Analysis (1999) The E1038G BRCA1 polymorphism in Greece, Meeting of the Breast Cancer Linkage Consortium, Amsterdam, The Netherlands, 29 November-1 December 1999.
33. Konstantopoulou I, Ladopoulou A., Pantazidis A, Kotsinas A., Gorgoulis V.G., Kittas C., Tsionou C., Minaretzis D., Voutsinas G., Athanassiadou A., Tzoracoelephtherakis E., Florentin L., Nounesis G., Chiotellis E. and D. Yannoukakos (1999) The E1038G BRCA1 polymorphism in Greece, 51st Meeting of the Hellenic Society of Biochemistry and Molecular Biology, Athens, Greece, 9-11 December 1999.
34. Voutsinas, G., V. Labropoulou, L. Psiouri, A. Papachatzopoulou, A. Vassiliou, E. Tzoracoeleftherakis, G.M. Maniatis and A. Athanassiadou (2000) Polymorphisms in genes CYP17, COMT, ER and breast cancer risk: a multigenic study on cancer susceptibility, Proceedings of the 22nd Meeting of the Hellenic Society of Biological Sciences, Skiathos, Greece, 25-28 May 2000, p. 296-297.
35. Voutsinas, G. (2000) Concurrent exposures to genotoxic agents: molecular targets and their relations in carcinogenesis, CCMS/NATO Pilot Study Meeting on Advanced Cancer Risk Assessment Methods, November 17-21, 2000, Santorini, Greece.
36. Puiu, L., O. Koveou, L. Psiouri, A. Papachatzopoulou, A. Kotsinas, V.G. Gorgoulis, E. Tzoracoeleftherakis, G.M. Maniatis, A. Athanassiadou and G. Voutsinas (2000) The CD95 (Fas/APO-1) death receptor pathway in breast cancer, Meeting of the Panhellenic Union of Biologists "Molecular Biology - Cytogenetics in Health", 8-10 December 2000, p. 146-147.
37. Kapranos, N., A. Stratigos, E. Petrakou, G. Voutsinas, A. Anastasiadou, E. Kokka, A. Pagouni, E. Christofidou, Ch. Antoniou and A. Katsambas (2001) p53 gene and protein analysis in non-melanoma skin cancer, Regional Meeting International Society of Dermatology, September 6-9, 2001, Rhodes, Greece.
38. Voutsinas G. (2001) Mutagenesis, Apoptosis: Basic relation to carcinogenic models, Folia Histochemica et Cytobiologica 39, Suppl. 1, 25.
39. Puiu, L., E. Petrakou, A. Apostolidou, L. Psiouri, A. Papachatzopoulou, E. Tzoracoeleftherakis, G.M. Maniatis, A. Athanassiadou and G. Voutsinas (2001) Fas (APO-1/CD95) gene structural alterations and transcript variant analysis in breast cancer, Proceedings of the 53rd Meeting of the Hellenic Society of Biochemistry and Molecular Biology, Athens, Greece, 13-15 December 2001, Newsletter 48, pp 344-348.
40. Fanourakis, G., S. Tseleni-Balafouta, A. Saetta, G. Voutsinas, M. Miaouli and P.S. Davaris (2002) p53 and Fas gene mutation detection and expression study in thyroid cancer, 8th Hellenic Conference of Pathology, Volos, Greece, 18-21 April 2002.
41. Petrakou, E., N. Kapranos, K. Anastasiadou, A. Stratigos, E. Kokka, E. Christofidou, A. Pagouni, A. Katsambas and G. Voutsinas (2002) p53 mutations and expression pattern in non-melanoma skin cancer, Proceedings of the 24th Meeting of the Hellenic Society of Biological Sciences, Eretria, Euboea Island, Greece, 23-26 May 2002, p. 237-238.
42. Puiu, L., E. Petrakou, A. Apostolidou, A. Athanassiadou and G. Voutsinas (2002) No mutations in Fas (APO-1/CD95) or a shift towards its soluble splice variant mRNA in breast cancer, Proceedings of the 17th Meeting of the European Association for Cancer Research, Granada, Spain, 8-11 June 2002, pp. 80-81.
43. Petrakou, E., N. Kapranos, K. Anastasiadou, A. Stratigos, E. Kokka, E. Christofidou, A. Pagouni, A. Katsambas and G. Voutsinas (2002) p53 mutations and expression pattern in non-melanoma skin cancer, Proceedings of the 17th Meeting of the European Association for Cancer Research, Granada, Spain, 8-11 June 2002, pp. 97.
44. Karoussos G, G. Voutsinas, A. Papachatzopoulou and A. Athanassiadou (2002) Analysis of allelic expression of the α-synuclein gene in Parkinson’s disease, Proceedings of the 17th Meeting of the Hellenic Society for Neuroscience, University of Crete, Rethymno, Greece, 4-6 October 2002, p. 52.
45. Apostolidou, A., N. Spyrou and G. Voutsinas (2003) Molecular epidemiology in cancer research, International Conference on Cancer Risk Assessment, 22-24 August 2003, Athens, Greece.
46. Sambani, C., R. La Starza, G. Voutsinas, H. Rigana, K. Manola, I. Wlodarska and C. Mecucci (2003) The unbalanced t(1;9) in myeloproliferative disorders is a recurrent rearrangement involving the satellite II family of chromosome 1 and the satellite III of chromosome 9, Annales de Génétique – International Journal of Human and Medical Genetics 46, 140-141.
47. Fanourakis, G., A. Goudopoulou, D. Sykoutri, C.S. Mitsiades, G. Voutsinas, S. Tseleni-Balafouta and N. Mitsiades (2003) B-RAF gene is a mutational target in human thyroid cancer, Proceedings of the 55th Meeting of the Hellenic Society of Biochemistry and Molecular Biology, Athens, Greece, 13-15 November 2003, Newsletter 50, pp 168-172.
48. Labropoulou, V., D. Stefanou, V. Douris, E Adronopoulou, A. Apostolidou, G. Voutsinas and K. Iatrou (2005) Endoparasitization of lepidopteran insects by hymenopterans: proteins of the endosymbiotic bracovirus of the parasitic wasp Cotesia congregata interact with immunity-related hemocyte proteins of the parasitized host Manduca sexta, Proceedings of the 27th Meeting of the Hellenic Society of Biological Sciences, Nafplion, Greece, 12-14 May 2005.
49. Tseleni-Balafouta, S., G. Fanourakis, G. Voutsinas, H. Litsiou, C. Mitsiades, N. Mitsiades and E. Patsouris (2005) Fibrilin 1 expression in thyroid carcinomas, Virchows Archiv 447 (2), 426.
50. Parcharidou, A., D. Lianou, P. Pavlopoulos, G. Voutsinas and C. Sambani (2005) A new mutation in the cubilin gene, responsible for the appearance of congenital juvenile megaloblastic anaemia and proteinuria in brothers, Haema 8 supplement, p. 445.
51. Nikas, V., H. Pratsinis, G. Vlahos, A. Antsaklis, D. Kletsas and G. Voutsinas (2006) Targeted chemotherapy in ovarian epithelial cancer, Proceedings of the 28th Meeting of the Hellenic Society of Biological Sciences, Ioannina, Greece, 18-20 May 2006, p. 289-290.
52. Anastasiou D., H. Pratsinis, K. Livadas, G. Alivizatos, D. Kletsas and G. Voutsinas (2006) Inhibition oh Hsp90 in bladder cancer, Proceedings of the 28th Meeting of the Hellenic Society of Biological Sciences, Ioannina, Greece, 18-20 May 2006, p. 7-8.
53. Kachrilas, S., K. Livadas, G. Alivizatos and G. Voutsinas (2006) Study of the structure and expression of PIK3CA in urinary bladder cancer, Proceedings of the 28th Meeting of the Hellenic Society of Biological Sciences, Ioannina, Greece, 18-20 May 2006, p. 151-152.
54. Tseleni-Balafouta, S., E. Sozopoulos, H. Litsiou, G. Voutsinas, G. Fanourakis, N. Mitsiades, K. Mitsiades and E. Patsouris (2006) Mutational analysis of the BRAF gene in human adrenocortical carcinomas, Virchows Archiv 448, P194.
55. Tseleni-Balafouta, S., H. Litsiou, E. Sozopoulos, G. Voutsinas, G. Fanourakis, N. Mitsiades, K. Mitsiades and E. Patsouris (2006) EGFR mutations in thyroid carcinoma, Pathological Anatomy Archives 20, p. 154, P025.
56. Kachrilas, S., D. Anastasiou, K. Livadas, G. Alivizatos, A. Papatsoris, I. Kastriotis and G. Voutsinas (2006) Mutation detection and expression study of the gene PIK3CA in urothelial bladder cancer, Proceedings of the 18th Panhellenic Congress of Urology, of the Hellenic Urological Society, Rhodes, Greece, 27 September-1 October 2006, p. 128-129, P29.
57. Voutsinas, G. (2006) From phenotype to genotype: the example of Tuberous Sclerosis, 2nd Congress of the Greek Alliance for Rare Diseases, "Childhood – Rare Diseases – Orphan Drugs", Athens, Greece, 23-24 November 2006.
58. Nikas, V., H. Pratsinis, S. Kachrilas, G. Vlahos, A. Antsaklis, D. Kletsas and G. Voutsinas (2006) Effect of targeted chemotherapeutic drugs on epithelial cancer cells of the ovary, 6th Panhellenic Congress on Cancer Markers and Targeted Therapy, Athens, Greece, 23-25 November 2006.
59. Kachrilas, S., D. Anastasiou, V. Nikas, K. Livadas, G. Alivizatos and G. Voutsinas (2006) Structure and expression of the PIK3CA gene in urothelial bladder cancer, 6th Panhellenic Congress on Cancer Markers and Targeted Therapy, Athens, Greece, 23-25 November 2006.
60. Voutsinas, G. (2007) Gene therapy – The future, 7th Meeting of Dermatology of the 3rd Clinic of Dermatology, Syngros Hospital, Athens, Greece, 28 April 2007, p. 18.
61. Anastasiou, D., D.J. Stravopodis, S. Melachrinou, P. Karkoulis, E. Konstantakou, A. Lampidonis, D. Kletsas and G. Voutsinas (2007) Functional inhibition of Hsp90 has no effect on the levels of extracellular matrix gene transcription in human bladder cancer cells, 9th Annual Meeting of the Hellenic Research Club for Connective Tissue and Matrix Biology, Athens, Greece, p.12.
62. Kitsos, C.P., M.S. Chalikias and G. Voutsinas (2007) A quantitative approach to breast cancer data, International Conference on Cancer Risk Assessment 2 (ICCRA2), Sandorini, Greece, 25-27 May 2007, p. 1-11.
63. Tseleni-Balafouta, S., H. Litsiou, G. Fanourakis, E. Sozopoulos, G. Voutsinas, N. Mitsiades, K. Mitsiades and E. Patsouris (2007) BRAF, EGFR and MET mutations in thyroid carcinoma, 4th Scientific Congress of the Athens Medical School, Athens, 1-2 June 2007, p. 128-129, A7.
64. Louverdi, C., G. Voutsinas, E. Litsiou, E. Patsouris, and S. Tseleni-Balafouta (2007) Mutational analysis of the BRAF gene in various conditions of the parathyroid glands, Virchows Archiv 451, 273 (PPI-249).
65. Litsiou, E., G. Fanourakis, S. Vernadakis, A. Vintila, G. Voutsinas, E. Patsouris and S. Tseleni-Balafouta (2007) RET/PTC rearrangements in Greek patients with papillary thyroid carcinoma, Virchows Archiv 451, 273 (PPI-250).
66. Vrtel, R., G. Voutsinas and R. Vodicka (2007) Tuberous Sclerosis – Development of valid diagnostic methods at a minimum cost, Mutation Detection – IX International Symposium on Mutations in the Genome, 23-27 September 2007, Xiamen, China, p. 59, P24.
67. Lampidonis, A., A. Argyrokastritis, D. Stravopodis, G. Voutsinas, L.H. Margaritis, I. Bizelis and E. Rogdakis (2007) Structural characterization and functional analysis of the promoter region of Hormone-Sensitive Lipase (HSL) gene of the sheep (Ovis aries), Animal Science Review 33, 30-31.
68. Gioni, V., T. Karabinas, G. Voutsinas, A.E. Roussidis, S. Papadopoulos, N.K. Karamanos and D. Kletsas (2007) Imatinib mesylate inhibits the proliferation and collagen synthesis in human breast stromal fibroblasts, 59th Meeting of the Hellenic Society of Biochemistry and Molecular Biology, 7-9 December 2007, Athens, Greece, p. 107.
69. Vrtel, R., G. Voutsinas, R. Vodicka, H. Filipova, D. Konvalinka, A. Santava and J. Santavy (2008) Development of reliable and economical DNA diagnostics in tuberous sclerosis, Fifth International Symposium on Genetics, Health and Disease (V-ISGHD), February 17-19, 2008, Amritsar, India, p. 74, P54.
70. Avgeris, S., R. Vrtel, D. Anastasiou, P. Papadopoulou, R. Vodicka, E. Anastasiadou, D.J. Stravopodis and G.E. Voutsinas (2008) Development of a protocol for molecular diagnosis of tuberous sclerosis, Proceedings of the 30th Scientific Conference of Hellenic Association for Biological Sciences, 22-24 May 2008, Thessaloniki, Greece, p. 40-41.
71. Stravopodis, D.J., D. Wang, I.S. Papasideri, L.H. Margaritis and G.E. Voutsinas (2008) Reconstitution of erythropoietin signalling pathway in non-erythroid cellular environment, Proceedings of the 30th Scientific Conference of Hellenic Association for Biological Sciences, 22-24 May 2008, Thessaloniki, Greece, p. 454-455.
72. Vrtel, R., H. Filipova, R. Vodicka, G. Voutsinas, D. Konvalinka, A. Santava and J. Santavy (2008) DNA diagnostics in tuberous sclerosis - development of reliable and economical test, 40th European Human Genetics Conference (ESHG 2008), May 31-June 3, 2008, Barcelona, Spain, P06.290.
73. Stavropoulou, C., Ε. Rigana, V.Ν. Georgakakos, G. Voutsinas, Κ.Ν. Manola, G. Pantelias, V. Makropoulos, Α. Symeonidis, Α. Kouraklis, Ν. Zoumbos , Ν. Vyniou, Ε. Plata, A. Galanopoulos, T. Marinakis, Ν. Anagnostopoulos, P. Roussou, Α. Fragou, Α. Parcharidou, V. Papa, Α. Lazaridou, C. Mitsouli, C. Megalakaki, Μ. Bakiri, Ν. Laoutaris, H. Papadaki, G. Bourikas, Μ. Protopappa, D. Georgiadou, P. Zikos, C. Sambani (2008) Polymorphisms of detoxification genes in patients with primary myelodysplastic syndrome, 19th Panhellenic Hematological Congress, November 19-22, 2008, Athens, Greece.
74. Gioni, V., T. Karabinas, G. Voutsinas, A.E. Roussidis, S. Papadopoulos, N.K. Karamanos and D. Kletsas (2009) Imatinib mesylate inhibits proliferation and collagen synthesis in human breast stromal fibroblasts, 15th Panhellenic Congress of Clinical Oncology, March 26-28, 2009, Athens, Greece.
75. Stavropoulou, C., S. Zachaki, K. Manola, G. Voutsinas, H. Orphanidou, V. Georgakakos and C. Sambani (2009) Association of NQO1 C609T polymorphism with chromosomes 5 and/or 7 abnormalities in patients with MDS/AML, 10th International Symposium on Myelodysplastic Syndromes, May 6-9, 2009, Patras, Greece, Leukemia Research 33, suppl. 1, S45-S46.
76. Anastasiou, D.K., D.J. Stravopodis and G.E. Voutsinas (2009) DNA methyltransferase and histone deacetylase inhibitors synergize to induce apoptotic death in human urinary bladder cancer cells, Proceedings of the 31st Scientific Conference of Hellenic Association for Biological Sciences, 14-16 May 2009, Patras, Greece, p. 14-15.
77. Gioni, V., Th. Karabinas, G. Voutsinas, A.E. Roussidis, S. Papadopoulos, N.K. Karamanos and D. Kletsas (2009) Imatinib mesylate inhibits the proliferation and collagen synthesis in human breast stromal fibroblasts, Proceedings of the 31st Scientific Conference of Hellenic Association for Biological Sciences, 14-16 May 2009, Patras, Greece, p. 60-61.
78. Karkoulis, P.K., D.J. Stravopodis, E.G. Konstantakou, L.H. Margaritis and G.E. Voutsinas (2009) 17-AAG induces cell cycle arrest and apoptosis in human urinary bladder cancer cell lines due to down-regulation of multiple Hsp90 clients in the Akt signalling pathway, Proceedings of the 31st Scientific Conference of Hellenic Association for Biological Sciences, 14-16 May 2009, Patras, Greece, p. 124-125.
79. Konstantakou, E.G., G.E. Voutsinas, P.K. Karkoulis, G. Aravantinos, L.H. Margaritis and D.J. Stravopodis (2009) Cisplatin-induced apoptosis of human bladder cancer cells is associated with p53-dependent and p53-independent regulatory responses, Proceedings of the 31st Scientific Conference of Hellenic Association for Biological Sciences, 14-16 May 2009, Patras, Greece, p. 172-173.
80. Setta-Kaffetzi, N., A. Thanasopoulou, M. Roumpelaki, A. Samara, E.G. Konstantakou, G.E. Voutsinas, N. Anagnou, K. Dimas, D.J. Stravopodis and E. Anastasiadou (2009) Xenograft animal models for the in vivo live imaging of human tumors, Proceedings of the 31st Scientific Conference of Hellenic Association for Biological Sciences, 14-16 May 2009, Patras, Greece, p. 318-319.
81. Voutsinas G.E. and Stravopodis D.J. (2009) Molecular targeting and gene delivery in bladder cancer therapy, 3rd Seminar of the Balkan Society of Oncology, 10-12 September 2009, Volos, Greece.
82. Karkoulis P.K., Stravopodis D.J., Konstantakou E.G., Melachroinou S., Anastasiou D., Margaritis L.H. and Voutsinas G.E. (2009) Hsp90 drug targeting in bladder cancer cells, 14th World Congress on Advances in Oncology and 12th International Symposium on Molecular Medicine, 15-17 October 2009, Loutraki, Greece, International Journal of Molecular Medicine 24 (suppl), S31.
83. Karkoulis P.K., Stravopodis D.J., Margaritis L.H. and Voutsinas G.E. (2009) Inhibition of multiple signaling pathways by 17-allylamino-17-demethoxygeldanamycin in human urinary bladder cancer cells, 60th Meeting of the Hellenic Society of Biochemistry and Molecular Biology, 20-22 November 2009, Athens, Greece, p. 137.
84. Karkoulis P.K., Stravopodis D.J., Margaritis L.H. and Voutsinas G.E. (2009) Pharmacological targeting of Hsp90 molecular chaperone in human urinary bladder cancer cells, 1st International Conference on Molecular Cancer Research, 27-29 November 2009, Athens, Greece, p. 32.
85. Karkoulis P.K., Stravopodis D.J., Velentzas A.D. and Voutsinas G.E. (2011) 17-DMAG induces functional impairment of multiple heat shock protein 90-assisted signaling pathways in human urinary bladder cancer cells, 62nd Conference of the Greek Society for Biochemistry and Molecular Biology, 9-11 December 2011, Athens, Greece.
86. Voutsinas, G., J. Traeger-Synodinos, D. Stardelis, A. Grypari, R. Rodopoulou, D. Synodinos, S. Youroukos, M. Lambrou, D. Yannoukakos (2012) A patient-initiated registry for Rare Diseases: the experience of the Greek Alliance for Rare Diseases (PESPA), 6th European Conference on Rare Diseases & Orphan Products, 23-25 May 2012, Brussels, Belgium.


Journal articles

2013	DOI PMID P K Karkoulis, D J Stravopodis, E G Konstantakou, G E Voutsinas (2013) Targeted inhibition of heat shock protein 90 disrupts multiple oncogenic signaling pathways, thus inducing cell cycle arrest and programmed cell death in human urinary bladder cancer cell lines. Cancer Cell Int. 13: 1. 11 Feb 8 Abstract: Notes:
	DOI PMID A V Stavropoulou, F Fostira, M Pertesi, M Tsitlaidou, G E Voutsinas, O Triantafyllidou, A Bamias, M A Dimopoulos, E Timotheadou, D Pectasides, C Christodoulou, G Klouvas, C Papadimitriou, T Makatsoris, G Pentheroudakis, G Aravantinos, V Karydakis, D Yannoukakos, G Fountzilas, I Konstantopoulou (2013) Prevalence of BRCA1 Mutations in Familial and Sporadic Greek Ovarian Cancer Cases. PLoS One. 8: 3. e58182 Epub 2013 Mar 11. Abstract: Notes:
2012	PMID K Pliarchopoulou, G Voutsinas, G Papaxoinis, K Florou, M Skondra, K Kostaki, P Roussou, K Syrigos, D Pectasides (2012) Correlation of CYP1A1, GSTP1 and GSTM1 gene polymorphisms and lung cancer risk among smokers. Oncol Lett. 3: 6. 1301-1306 Jun Abstract: Notes:
2011	DOI PMID Dimitrios J Stravopodis, Panagiotis K Karkoulis, Eumorphia G Konstantakou, Sophia Melachroinou, Angeliki Thanasopoulou, Gerasimos Aravantinos, Lukas H Margaritis, Ema Anastasiadou, Gerassimos E Voutsinas (2011) Thymidylate synthase inhibition induces p53-dependent and p53-independent apoptotic responses in human urinary bladder cancer cells. J Cancer Res Clin Oncol 137: 2. 359-374 Feb Abstract: In search for more effective clinical protocols, the antimetabolite drug 5-fluorouracil (5-FU) has been successfully included in new regimens of bladder cancer combination chemotherapy. In the present study, we have investigated the effects of 5-FU treatment on apoptosis induction in wild-type and mutant p53 urinary bladder cancer cells. Notes:
	DOI PMID Antonis D Lampidonis, Emmanuel Rogdakis, Gerassimos E Voutsinas, Dimitrios J Stravopodis (2011) The resurgence of Hormone-Sensitive Lipase (HSL) in mammalian lipolysis. Gene 477: 1-2. 1-11 May Abstract: The ability to store energy in the form of energy-dense triacylglycerol and to mobilize these stores rapidly during periods of low carbohydrate availability or throughout the strong metabolic demand is a highly conserved process, absolutely essential for survival. In the industrialized world the regulation of this pathway is viewed as an important therapeutic target for disease prevention. Adipose tissue lipolysis is a catabolic process leading to the breakdown of triacylglycerols stored in fat cells, and release of fatty acids and glycerol. Mobilization of adipose tissue fat is mediated by the MGL, HSL and ATGL, similarly functioning enzymes. ATGL initiates lipolysis followed by the actions of HSL on diacylglycerol, and MGL on monoacylglycerol. HSL is regulated by reversible phosphorylation on five critical residues. Phosphorylation alone, however, is not enough to activate HSL. Probably, conformational alterations and a translocation from the cytoplasm to lipid droplets are also involved. In accordance, Perilipin functions as a master regulator of lipolysis, protecting or exposing the triacylglycerol core of a lipid droplet to lipases. The prototype processes of hormonal lipolytic control are the Î²-adrenergic stimulation and suppression by insulin, both of which affect cytoplasmic cyclic AMP levels. Lipolysis in adipocytes is an important process in the management of body energy reserves. Its deregulation may contribute to the symptoms of type 2 diabetes mellitus and other pathological situations. We, herein, discuss the metabolic regulation and function of lipases mediating mammalian lipolysis with a focus on HSL, quoting newly identified members of the lipolytic proteome. Notes:

2010	DOI PMID Gerassimos E Voutsinas, Eleana F Stavrou, Gerassimos Karousos, Aggeliki Dasoula, Adamantia Papachatzopoulou, Maria Syrrou, Annemieke J M H Verkerk, Peter van der Spek, George P Patrinos, Reinhard Stöger, Aglaia Athanassiadou (2010) Allelic imbalance of expression and epigenetic regulation within the alpha-synuclein wild-type and p.Ala53Thr alleles in Parkinson disease. Hum Mutat 31: 6. 685-691 Jun Abstract: Genetic alterations in the alpha-synuclein (SNCA) gene have been implicated in Parkinson Disease (PD), including point mutations, gene multiplications, and sequence variations within the promoter. Such alterations may be involved in pathology through structural changes or overexpression of the protein leading to protein aggregation, as well as through impaired gene expression. It is, therefore, of importance to specify the parameters that regulate SNCA expression in its normal and mutated state. We studied the expression of SNCA alleles in a lymphoblastoid cell line and in the blood cells of a patient heterozygous for p.Ala53Thr, the first mutation to be implicated in PD pathogenesis. Here, we provide evidence that: (1) SNCA shows monoallelic expression in this patient, (2) epigenetic silencing of the mutated allele involves histone modifications but not DNA methylation, and (3) steady-state mRNA levels deriving from the normal SNCA allele in this patient exceed those of the two normal SNCA alleles combined, in matching, control individuals. An imbalanced SNCA expression in this patient is thus documented, with silencing of the p.Ala53Thr allele and upregulation of the wild-type-allele. This phenomenon is demonstrated for a first time in the SNCA gene, and may have important implications for PD pathogenesis. Notes:
	DOI PMID Panagiotis K Karkoulis, Dimitrios J Stravopodis, Lukas H Margaritis, Gerassimos E Voutsinas (2010) 17-Allylamino-17-demethoxygeldanamycin induces downregulation of critical Hsp90 protein clients and results in cell cycle arrest and apoptosis of human urinary bladder cancer cells. BMC Cancer 10: 09 Abstract: ABSTRACT: BACKGROUND: 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinone ansamycin antibiotic, specifically targets heat shock protein 90 (Hsp90) and interferes with its function as a molecular chaperone that maintains the structural and functional integrity of various protein clients involved in cellular signaling. In this study, we have investigated the effect of 17-AAG on the regulation of Hsp90-dependent signaling pathways directly implicated in cell cycle progression, survival and motility of human urinary bladder cancer cell lines. METHODS: We have used MTT-based assays, FACS analysis, Western blotting, semi-quantitative RT-PCR, immunocytochemistry and scratch-wound assay in RT4, RT112 and T24 human urinary bladder cancer cell lines. RESULTS: We have demonstrated that, upon 17-AAG treatment, bladder cancer cells are arrested in the G1 phase of the cell cycle and eventually undergo apoptotic cell death in a dose-dependent manner. Furthermore, 17-AAG administration was shown to induce a pronounced downregulation of multiple Hsp90 protein clients and other downstream effectors, such as IGF-IR, Akt, IKK-Î±, IKK-Î², FOXO1, ERK1/2 and c-Met, resulting in sequestration-mediated inactivation of NF-ÎºB, reduced cell proliferation and decline of cell motility. CONCLUSIONS: In total, we have clearly evinced a dose-dependent and cell type-specific effect of 17-AAG on cell cycle progression, survival and motility of human bladder cancer cells, due to downregulation of multiple Hsp90 clients and subsequent disruption of signaling integrity. Notes:
	DOI PMID Elias Sozopoulos, Helen Litsiou, Gerassimos Voutsinas, Nikolaos Mitsiades, Nikolaos Anagnostakis, Thomais Tseva, Efstratios Patsouris, Sofia Tseleni-Balafouta (2010) Mutational and immunohistochemical study of the PI3K/Akt pathway in papillary thyroid carcinoma in Greece. Endocr Pathol 21: 2. 90-100 Jun Abstract: PI3K/Akt signaling pathway plays critical role in many cell processes. There is indication that enhanced activation of PI3K/Akt cascade is implicated in thyroid tumors. Aim of this study was to evaluate the mutational status and expression of PI3K/Akt pathway mediators in papillary thyroid carcinoma in Greece. We evaluated the presence of mutations in PIK3CA (exons 9 and 20), AKT1 (exons 6-11), AKT2 (exons 6-11), AKT3 (exons 5-10), PTEN (exons 3-8), and PDPK1 (exons 4-10) genes in 83 papillary thyroid carcinomas by DNA sequencing. The expression levels of phospho-Akt and insulin-like growth factor I receptor (IGF-IR) were evaluated by immunohistochemistry. PIK3CA mutations were found in three samples. The analysis of AKT1 revealed one silent mutation in exon 9 (G726A) in 16 samples. One specimen carried an AKT3 mutation. One missense mutation was found in one sample in PTEN. No mutations were found in AKT2 and PDPK1. Increased levels of phosphorylated total Akt and IGF-IR were identified in some papillary cancers. Our findings indicate that PI3K/Akt signaling pathway is activated in some papillary tumors. However, mutations in genes coding most mediators of the pathway have not been proven to be the major modus of enhanced activation. These data suggest a potential role for PI3K/Akt-mediated signaling in papillary thyroid tumors. Notes:
2009	PMID Dimitrios J Stravopodis, Panagiotis K Karkoulis, Eumorphia G Konstantakou, Sophia Melachroinou, Antonis D Lampidonis, Dimitra Anastasiou, Stefanos Kachrilas, Niki Messini-Nikolaki, Issidora S Papassideri, Gerasimos Aravantinos, Lukas H Margaritis, Gerassimos E Voutsinas (2009) Grade-dependent effects on cell cycle progression and apoptosis in response to doxorubicin in human bladder cancer cell lines. Int J Oncol 34: 1. 137-160 Jan Abstract: Doxorubicin is an important component of combination therapy for muscle-invasive urinary bladder cancer. Treatment with this topoisomerase II poison is able to interfere with cell cycle progression and lead to cancer cell death. Using FACS analysis, Western immunoblotting and semi-quantitative RT-PCR, we studied the effects of doxorubicin on cell cycle progression and apoptosis, and also explored the possibility of using groups of genes as biomarkers of prognosis and/or response to doxorubicin treatment in human urinary bladder cancer cells. Doxorubicin induced dose-dependent G2/M and/or G1/S cell cycle arrest, followed by grade- and dose-dependent reduction in the amount of the cytosolic trimeric form of FasL, activation of Caspase-8, Caspase-9, Caspase-3, cleavage of PARP, Lamin A/C, Bcl-XL/S and interestingly Hsp90, and finally cell death. Data presented here also suggest the use of the expression patterns of Cyclin-E2, Cyclin-F, p63, p73, FasL, TRAIL, Tweak, Tweak-R, XAF-1, OPG and Bok genes for identification of the differentiation grade, and Cyclin-B2, GADD45A, p73, FasL, Bik, Bim, TRAIL, Fas, Tweak-R, XAF-1, Bcl-2, Survivin, OPG, DcR2 and Bcl-XL genes for the detection of response to doxorubicin in human bladder cancer cells. Notes:
	PMID G E Voutsinas, D J Stravopodis (2009) Molecular targeting and gene delivery in bladder cancer therapy. J BUON 14 Suppl 1: S69-S78 Sep Abstract: Urothelial carcinoma of the bladder is the second most common genitourinary malignancy and the second most common cause of genitourinary cancer-related deaths with a worldwide estimate of about 300,000 new cases diagnosed every year. A significant problem in this type of cancer is the high recurrence rate of non-invasive primary tumors, leading to a high percentage of tumor progression and to a very poor 5-year survival rate. Targeted and gene therapy are currently the two major efforts in cancer treatment. Targeted therapy refers to strategies against specific cellular molecules deregulated in tumors, whereas gene therapy focuses on the genetic modification of tumor cells, mainly for correcting gene defects, inducing selective tumor cell death or modulating host's immune response. Recent advances in our understanding of the pathogenesis of bladder cancer at the molecular level have provided a significant number of cellular targets for therapy and have shown the importance of individualized therapy according to the molecular profile exhibited by the tumor cells. While the major problems of both targeted and gene therapy are far from being solved yet, both lines of cancer therapy hold promising results. This article aims at providing a brief general overview of this broad subject. Notes:
	DOI PMID Vassiliki Kotoula, Elias Sozopoulos, Helen Litsiou, Galinos Fanourakis, Triantafyllia Koletsa, Gerassimos Voutsinas, Sophia Tseleni-Balafouta, Constantine S Mitsiades, Axel Wellmann, Nicholas Mitsiades (2009) Mutational analysis of the BRAF, RAS and EGFR genes in human adrenocortical carcinomas. Endocr Relat Cancer 16: 2. 565-572 Jun Abstract: The serine/threonine kinase B-Raf plays a key role in the Ras/Raf/MEK/ERK pathway that relays extracellular signals for cell proliferation and survival. Several types of human malignancies harbor activating BRAF mutations, most frequently a V600E substitution. The epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase (TK) receptor that mediates proliferation and survival signaling, is expressed in a wide variety of normal and neoplastic tissues. EGFR inhibitors have produced objective responses in patients with non-small cell lung carcinomas harboring activating EGFR TK domain somatic mutations. We evaluated the presence of mutations in BRAF (exons 11 and 15), KRAS (exons 1 and 2), NRAS (exons 1 and 2), and EGFR (exons 18-21) in adrenal carcinomas (35 tumor specimens and two cell lines) by DNA sequencing. BRAF mutations were found in two carcinomas (5.7%). Four carcinomas (11.4%) carried EGFR TK domain mutations. One specimen carried a KRAS mutation, and another carried two NRAS mutations. No mutations were found in the two adrenocortical cell lines. BRAF- and EGFR-mutant tumor specimens exhibited stronger immunostaining for the phosphorylated forms of the MEK and ERK kinases than their wild-type counterparts. EGFR-mutant carcinomas exhibited increased phosphorylation of EGFR (Tyr 992) compared with wild-type carcinomas. We conclude that BRAF, RAS, and EGFR mutations occur in a subset of human adrenocortical carcinomas. Inhibitors of the Ras/Raf/MEK/ERK and EGFR pathways represent candidate targeted therapies for future clinical trials in carefully selected patients with adrenocortical carcinomas harboring respective activating mutations. Notes:
	PMID Eumorphia G Konstantakou, Gerassimos E Voutsinas, Panagiotis K Karkoulis, Gerasimos Aravantinos, Lukas H Margaritis, Dimitrios J Stravopodis (2009) Human bladder cancer cells undergo cisplatin-induced apoptosis that is associated with p53-dependent and p53-independent responses. Int J Oncol 35: 2. 401-416 Aug Abstract: Cisplatin is a first-line chemotherapeutic agent and a powerful component of standard treatment regimens for several human malignancies including bladder cancer. DNA-Pt adducts produced by cisplatin are mainly responsible for cellular toxicity and induction of apoptosis. Identification of the mechanisms that control sensitivity to cisplatin is central to improving its therapeutic index and to successfully encountering the acquired resistance frequently emerging during therapy. In the present study, using MTT-based assays, Western blotting and semi-quantitative RT-PCR, we examined the apoptosis-related cellular responses to cisplatin exposure in two human urinary bladder cancer cell lines characterized by different malignancy grade and p53 genetic status. Both RT4 (grade I; wild-type p53) and T24 (grade III; mutant p53) cell types proved to be vulnerable to cisplatin apoptotic activity, albeit in a grade-dependent and drug dose-specific manner, as demonstrated by the proteolytic processing profiles of Caspase-8, Caspase-9, Caspase-3, and the Caspase repertoire characteristic substrates PARP and Lamin A/C, as well. The differential resistance of RT4 and T24 cells to cisplatin-induced apoptosis was associated with an RT4-specific phosphorylation (Ser15; Ser392) pattern of p53, together with structural amputations of the Akt and XIAP anti-apoptotic regulators. Furthermore, cisplatin administration resulted in a Granzyme B-mediated proteolytic cleavage of Hsp90 molecular chaperone, exclusively occurring in RT4 cells. To generate functional networks, expression analysis of a number of genes, including Bik, Bim, Bcl-2, FAP-1, Fas, FasL, TRAIL, Puma, Caspase-10, ATP7A, ATP7B and MRP1, was performed, strongly supporting the role of p53-dependent and p53-independent transcriptional responses in cisplatin-induced apoptosis of bladder cancer cells. Notes:
2008	DOI PMID Dimitrios J Stravopodis, Athanassios Z Zapheiropoulos, Gerassimos Voutsinas, Lukas H Margaritis, Issidora S Papassideri (2008) A PCR-based integrated protocol for the structural analysis of the 13th exon of the human beta-myosin heavy chain gene (MYH7): development of a diagnostic tool for HCM disease. Exp Mol Pathol 84: 3. 245-250 Jun Abstract: Familial Hypertrophic Cardiomyopathy (FHC) constitutes a genetic disease of the sarcomere characterized by a Mendelian pattern of inheritance. A variety of different mutations affecting the at least eight sarcomeric gene products has been identified and the majority of them appear to function through a dominant negative mechanism. Family history analysis and genetic counseling have been widely adopted as integral tools for the evaluation and management of individuals with Hypertrophic Cardiomyopathy (HCM). Genetic testing of the disease has been progressively released into the clinical mainstream, thus rendering the development of novel and potent molecular diagnostic protocols an inevitable task. To this direction, we have evolved an integrated PCR-based molecular protocol, which through the utilization of novel "exonic" primers allows, among others, the structural analysis of the 13th exon of the human beta-myosin heavy chain gene locus (MYH7) mainly characterized by the critical for HCM Arginine residue 403 (R(403)). Interestingly, through a DNA sequencing approach, a single nucleotide substitution from "G" to "T" was detected in the adjacent 13th intron, thus divulging the versatile potential of the present molecular protocol to clinical practice. Notes:
	DOI PMID C Stavropoulou, C Sambani, H Rigana, V N Georgakakos, G Voutsinas, K N Manola, G E Pantelias, V Makropoulos (2008) Low frequency of the glutathione-S-transferase T1-null genotype in patients with primary myelodysplastic syndrome and 5q deletion. Leukemia 22: 8. 1643-1646 Aug Abstract: Notes:
	DOI PMID Vassiliki Gioni, Theodoros Karampinas, Gerassimos Voutsinas, Andreas E Roussidis, Savvas Papadopoulos, Nikos K Karamanos, Dimitris Kletsas (2008) Imatinib mesylate inhibits proliferation and exerts an antifibrotic effect in human breast stroma fibroblasts. Mol Cancer Res 6: 5. 706-714 May Abstract: Tumor stroma plays an important role in cancer development. In a variety of tumors, such as breast carcinomas, a desmoplastic response, characterized by stromal fibroblast and collagen accumulation, is observed having synergistic effects on tumor progression. However, the effect of known anticancer drugs on stromal cells has not been thoroughly investigated. Imatinib mesylate is a selective inhibitor of several protein tyrosine kinases, including the receptor of platelet-derived growth factor, an important mediator of desmoplasia. Recently, we have shown that imatinib inhibits the growth and invasiveness of human epithelial breast cancer cells. Here, we studied the effect of imatinib on the proliferation and collagen accumulation in breast stromal fibroblasts. We have shown that it blocks the activation of the extracellular signal-regulated kinase and Akt signaling pathways and up-regulates cyclin-dependent kinase inhibitor p21(WAF1), leading to the inhibition of fibroblast proliferation, by arresting them at the G(0)/G(1) phase of the cell cycle. Imatinib inhibits more potently the platelet-derived growth factor-mediated stimulation of breast fibroblast proliferation. By using specific inhibitors, we have found that this is due to the inhibition of the Akt pathway. In addition, imatinib inhibits fibroblast-mediated collagen accumulation. Conventional and quantitative PCR analysis, as well as gelatin zymography, indicates that this is due to the down-regulation of mRNA synthesis of collagen I and collagen III-the main collagen types in breast stroma-and not to the up-regulation or activation of collagenases matrix metalloproteinase 2 and matrix metalloproteinase 9. These data indicate that imatinib has an antifibrotic effect on human breast stromal fibroblasts that may inhibit desmoplastic reaction and thus tumor progression. Notes:

	DOI PMID Antonis D Lampidonis, Alexandros Argyrokastritis, Dimitrios J Stravopodis, Gerassimos E Voutsinas, Triantafyllia G Ntouroupi, Lukas H Margaritis, Iosif Bizelis, Emmanuel Rogdakis (2008) Cloning and functional characterization of the ovine Hormone Sensitive Lipase (HSL) full-length cDNAs: an integrated approach. Gene 416: 1-2. 30-43 Jun Abstract: Hormone Sensitive Lipase (HSL) is a highly regulated enzyme that mediates lipolysis in adipocytes. HSL enzymatic activity is increased by adrenergic agonists, such as catecholamines and glucagons, which induce cyclic AMP (cAMP) intracellular production, subsequently followed by the activation of Protein Kinase A (PKA) and its downstream signalling cascade reactions. Since HSL constitutes the key enzyme in the regulation of lipid stores and the only enzyme being subjected to hormonal regulation [in terms of the recently identified Adipose Triglyceride Lipase (ATGL)], the ovine Hormone Sensitive Lipase (ovHSL) full-length cDNA clones were isolated, using a Polymerase Chain Reaction-based (PCR) strategy. The two isolated isoforms ovHSL-A and ovHSL-B contain two highly homologous Open Reading Frame (ORF) regions of 2.089 Kb and 2.086 Kb, respectively, the latter having been missed the 688th triplet coding for glutamine (DeltaQ(688)). The putative 695 and 694 amino acid respective sequences bear strong homologies with other HSL protein family members. Southern blotting analysis revealed that HSL is represented as a single copy gene in the ovine genome, while Reverse Transcription-PCR (RT-PCR) approaches unambiguously dictated its variable transcriptional expression profile in the different tissues examined. Interestingly, as undoubtedly corroborated by both RT-PCR and Western blotting analysis, ovHSL gene expression is notably enhanced in the adipose tissue during the fasting period, when lipolysis is highly increased in ruminant species. Based on the crystal structure of an Archaeoglobus fulgidus enzyme, a three-dimensional (3D) molecular model of the ovHSL putative catalytic domain was constructed, thus providing an inchoative insight into understanding the enzymatic activity and functional regulation mechanisms of the ruminant HSL gene product(s). Notes:
	DOI PMID Antonis D Lampidonis, Dimitrios J Stravopodis, Gerassimos E Voutsinas, Niki Messini-Nikolaki, George C Stefos, Lukas H Margaritis, Alexandros Argyrokastritis, Iosif Bizelis, Emmanuel Rogdakis (2008) Cloning and functional characterization of the 5' regulatory region of ovine Hormone Sensitive Lipase (HSL) gene. Gene 427: 1-2. 65-79 Dec Abstract: Hormone Sensitive Lipase (HSL) catalyzes the rate-limiting step in the mobilization of fatty acids from adipose tissue, thus determining the supply of energy substrates in the body. HSL enzymatic activity is increased by adrenergic agonists, such as catecholamines and glucagons, which induce cyclic AMP (cAMP) intracellular production, subsequently followed by the activation of Protein Kinase A (PKA) and its downstream signaling cascade reactions. HSL constitutes the critical enzyme in the modulation of lipid stores and the only component being subjected to hormonal control in terms of the recently identified Adipose Triglyceride Lipase (ATGL). In order to acquire detailed knowledge with regard to the mechanisms regulating ovine HSL (ovHSL) gene transcription activity, we initially isolated and cloned the 5' proximal and distal promoter regions through a genome walking approach, with the utilization of the already characterized ovHSL cDNAs. As evinced by BLAST analysis and a multiple alignment procedure, the isolated genomic fragment of 2.744 kb appeared to contain the already specified 5'-untranslated region (5'-UTR), which was interrupted by a relatively large intron of 1.448 kb. Regarding the upstream remaining part of 1.224 kb, it was demonstrated to represent a TATA-less promoter area, harboring several cis-regulatory elements that could be putatively recognized by relatively more general transcription factors, mainly including Stimulating protein 1 (Sp1), CCAAT-box Binding Factors (CBFs), Activator Protein 2 (AP2) and Glucocorticoid Receptor (GR), as well as other cis-acting regions denominated as Insulin Response Element (IRE), Glucose Response Element (GRE), Fat Specific Element (FSE) and cAMP Response Element (CRE), which could likely function in a nourishment (i.e. glucose)-/hormone-dependent fashion. When different genomic fragments were directionally (5' to 3') cloned into a suitable reporter vector upstream of a promoter-less luciferase gene and transiently transfected into 3T3-L1 (mouse fibroblasts) as well as T24 (human bladder cancer) cell lines, strong promoter activities were unambiguously detected, with the -140/+18 nucleotide sequence bearing the highest transcriptional response, thus indicating that the 1.224 kb 5' flanking region, isolated by genome walking, veritably contains the ovHSL gene promoter. Of particular significance are the observations that the functional promoter fragments could trigger the transcriptional activity of luciferase gene only under high concentration of glucose conditions in both cell lines. Notes:
2007	DOI PMID Constantine S Mitsiades, Joseph Negri, Ciaran McMullan, Douglas W McMillin, Elias Sozopoulos, Galinos Fanourakis, Gerassimos Voutsinas, Sophia Tseleni-Balafouta, Vassiliki Poulaki, David Batt, Nicholas Mitsiades (2007) Targeting BRAFV600E in thyroid carcinoma: therapeutic implications. Mol Cancer Ther 6: 3. 1070-1078 Mar Abstract: B-Raf is an important mediator of cell proliferation and survival signals transduced via the Ras-Raf-MEK-ERK cascade. BRAF mutations have been detected in several tumors, including papillary thyroid carcinoma, but the precise role of B-Raf as a therapeutic target for thyroid carcinoma is still under investigation. We analyzed a panel of 93 specimens and 14 thyroid carcinoma cell lines for the presence of BRAF mutations and activation of the mitogen-activated protein/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. We also compared the effect of a B-Raf small inhibitory RNA construct and the B-Raf kinase inhibitor AAL881 on both B-Raf wild-type and mutant thyroid carcinoma cell lines. We found a high prevalence of the T1799A (V600E) mutation in papillary and anaplastic carcinoma specimens and cell lines. There was no difference in patient age, B-Raf expression, Ki67 immunostaining, or clinical stage at presentation between wild-type and BRAF(V600E) specimens. Immunodetection of phosphorylated and total forms of MEK and ERK revealed no difference in their phosphorylation between wild-type and BRAF(V600E) patient specimens or cell lines. Furthermore, a small inhibitory RNA construct targeting the expression of both wild-type B-Raf and B-Raf(V600E) induced a comparable reduction of viability in both wild-type and BRAF(V600E) mutant cancer cells. Interestingly, AAL881 inhibited MEK and ERK phosphorylation and induced apoptosis preferentially in BRAF(V600E)-harboring cells than wild-type ones, possibly because of better inhibitory activity against B-Raf(V600E). We conclude that B-Raf is important for the pathophysiology of thyroid carcinomas irrespective of mutational status. Small molecule inhibitors that selectively target B-Raf(V600E) may provide clinical benefit for patients with thyroid cancer. Notes:
	PMID Dimitrios J Stravopodis, Lukas H Margaritis, Gerassimos E Voutsinas (2007) Drug-mediated targeted disruption of multiple protein activities through functional inhibition of the Hsp90 chaperone complex. Curr Med Chem 14: 29. 3122-3138 Abstract: Hsp90 is an evolutionarily conserved and ubiquitously expressed molecular chaperone that mainly modulates, along with a group of co-chaperones, the general platform of protein folding and prevents the nonspecific aggregation of misfolded or unfolded proteins. In the voluminous Hsp90 clientele, a large variety of important regulatory proteins can be identified, including many whose deregulation may lead to cancer initiation and progression, such as the oncogenic clients pp60(v-src), Bcr-Abl, mutated p53, ErbB2 (Her-2), Akt, Flt3, HIF-1alpha and B-Raf. Therefore, inhibition of Hsp90 function offers the prospect of simultaneously disrupting multiple signaling pathways directly implicated in the development of malignant phenotypes. During the last few years, there has been a major focus on the development of Hsp90 specific inhibitors. This started with the discovery that certain natural products could specifically disrupt Hsp90 chaperone activities. The benzoquinone ansamycin antibiotic geldanamycin and its less toxic derivative 17-AAG have been shown to possess strong anti-proliferative and apoptotic activity in cancer cells, whereas 17-AAG has demonstrated potent anti-tumor activity in several human xenograft models, including breast, prostate and colon cancer. In an effort to overcome difficulties with drug toxicity and solubility, a number of novel bioengineered 17-AAG analogues, such as 17-DMAG and IPI-504, and small-molecule inhibitors, including purine and pyrazole derivatives, have emerged from rational drug design followed by high-throughput screening approaches. 17-AAG was the leader inhibitor to enter and successfully complete phase I clinical trials, thus demonstrating that Hsp90 constitutes a valid drug target for cancer therapy. This review includes information on the current model of ternary interactions between Hsp90, client proteins and a vast array of co-chaperones followed by a list of characteristic inhibitors and ongoing clinical trials reported thus far. Notes:
	DOI PMID C Stavropoulou, D Korakaki, H Rigana, G Voutsinas, M Polyzoi, V N Georgakakos, K N Manola, C E Karageorgiou, C Sambani (2007) Glutathione-S-transferase T1 and M1 gene polymorphisms in Greek patients with multiple sclerosis: a pilot study. Eur J Neurol 14: 5. 572-574 May Abstract: Oxidative stress has been implicated in the pathogenesis of multiple sclerosis (MS). Glutathione-S-transferases (GSTs) are detoxification enzymes, evolved to protect cells against reactive oxygen metabolites. Both GSTT1 and GSTM1 genes exhibit a homozygous deletion polymorphism (null genotype) leading to abolished enzyme activity. We studied the impact of the GSTT1 and GSTM1 polymorphisms on MS susceptibility in a case-control study of 47 Greek patients and 165 controls. Correlations between genotype, gender and disability status were also investigated. The incidence of both GSTT1 and GSTM1 genotypes did not differ significantly between controls and patients. A significantly increased frequency of GSTM1 null genotype was found amongst female patients (65.5%) as compared with males (33.3%, P =0.04). The results suggest that GSTT1 and GSTM1 have no major pathogenetic role on the MS occurrence, nor any strong modifying effect on the disability status. The higher incidence of GSTM1 null genotype observed in female patients, suggests a possible role of the GSTM1 detoxification pathway in a gender-dependent manner. Notes:
2006	DOI PMID S Tseleni-Balafouta, H Gakiopoulou, G Fanourakis, G Voutsinas, D Balafoutas, E Patsouris (2006) Tenascin-C protein expression and mRNA splice variants in thyroid carcinoma. Exp Mol Pathol 80: 2. 177-182 Apr Abstract: Tenascin-C (Tn-C) is a matricellular protein involved in the initial and intermediate stages of cell adhesion. The present study is the first undertaken to comparatively investigate Tn-C in neoplastic, non-neoplastic thyroid lesions and normal thyroid tissues. Forty-eight thyroid specimens were studied immunohistochemically using a monoclonal antibody against Tn-C. Immunohistochemistry was supplemented by RT-PCR analysis of the two Tn-C mRNA splice variants in 13 thyroid cancer cell lines. Normal and non-neoplastic tissues were devoid of Tn-C, as well as follicular neoplasms, Huerthle-cell and anaplastic carcinomas. Most papillary carcinomas showed a focally intensive extracellular staining, localized in the connective tissue stroma, whereas most medullary carcinomas showed a staining in the connective tissue but also in intracellular location mainly. RT-PCR analysis detected Tn-C mRNA in all thyroid cancer cell lines with prevalence of the large splice variant in all but the medullary line, characterized by a higher Tn-Csmall:Tn-Clarge ratio. In conclusion, Tn-C re-expression has been observed in papillary and medullary thyroid carcinomas with different staining patterns accompanied by the prevalence of different mRNA splice variants in cell cultures. It seems possible that Tn-C is rather synthesized by tumor cells than by activated stromal cells. Notes:
	DOI PMID Constantine S Mitsiades, Vassiliki Kotoula, Vassiliki Poulaki, Elias Sozopoulos, Joseph Negri, Elpida Charalambous, Galinos Fanourakis, Gerassimos Voutsinas, Sophia Tseleni-Balafouta, Nicholas Mitsiades (2006) Epidermal growth factor receptor as a therapeutic target in human thyroid carcinoma: mutational and functional analysis. J Clin Endocrinol Metab 91: 9. 3662-3666 Sep Abstract: CONTEXT: The epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase (TK) receptor that mediates proliferation and survival signaling, is expressed in a wide variety of normal and neoplastic tissues. EGFR inhibitors have produced objective responses in patients with non-small-cell lung carcinomas harboring activating EGFR TK domain somatic mutations. OBJECTIVE AND METHODS: Because the EGFR pathway has been reported to be important for the pathophysiology of thyroid carcinoma, we investigated the expression and mutational status of EGFR in 14 thyroid carcinoma cell lines as well as its functional role by evaluating their in vitro sensitivity to AEE788, a new dual-family EGFR/ErbB2 and vascular endothelial growth factor receptor TK inhibitor. We also evaluated the mutational status, mRNA and protein expression, as well as phosphorylation status of EGFR in a panel of thyroid carcinoma specimens. RESULTS: EGFR expression and phosphorylation in the thyroid carcinoma cell lines and tissue specimens were present but not stronger than in noncancerous thyroid tissue. EGFR TK domain mutations were detected in two of 62 histological specimens (3.2%) but not in cell lines. All thyroid carcinoma cell lines were significantly less sensitive (IC(50) at least 25-fold higher) in vitro to AEE788 than a primary culture of EGFR-mutant lung carcinoma cells. CONCLUSIONS: Thyroid carcinoma cells overall are poorly responsive to clinically relevant concentrations of AEE788 in vitro. The presence of EGFR-activating TK domain mutations may identify a small minority of thyroid cancer patients that may benefit from EGFR inhibitors, but additional preclinical evidence of efficacy is needed. Notes:
	DOI PMID Constantine S Mitsiades, Vassiliki Poulaki, Galinos Fanourakis, Elias Sozopoulos, Douglas McMillin, Zhaoqin Wen, Gerassimos Voutsinas, Sophia Tseleni-Balafouta, Nicholas Mitsiades (2006) Fas signaling in thyroid carcinomas is diverted from apoptosis to proliferation. Clin Cancer Res 12: 12. 3705-3712 Jun Abstract: PURPOSE: The death receptor Fas is present in thyroid carcinomas, yet fails to trigger apoptosis. Interestingly, Fas has been reported to be actually overexpressed in papillary thyroid carcinomas, suggesting that it may confer a survival advantage. EXPERIMENTAL DESIGN: We investigated the expression and activation status of Fas pathway mediators in thyroid carcinoma cell lines and tumor specimens. RESULTS: All cell lines tested express Fas-associated death domain, procaspase-8, procaspase-9, and procaspase-3; resistance to Fas-mediated apoptosis could not be attributed to lack of any of these apoptosis mediators. Moreover, Fas death domain mutations were not found in our study. The proteasome inhibitors MG132 and PS-341 (bortezomib, Velcade), which lead to accumulation of the nuclear factor kappaB (NF-kappaB) inhibitor IkappaB, did not sensitize SW579 cells to Fas-mediated apoptosis, suggesting that resistance to Fas-mediated apoptosis is not due to proteasome or NF-kappaB activity. Cross-linking of Fas in vitro induced recruitment of Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (FLIP) instead of procaspase-8. Inhibition of FLIP expression with a FLIP antisense oligonucleotide resulted in significant sensitization to Fas-mediated apoptosis. Fas cross-linking promoted BrdUrd incorporation; activated the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase, NF-kappaB, and activator protein-1 pathways in thyroid carcinoma cells in vitro; and protected cells from tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. We also found that good prognosis papillary thyroid carcinoma specimens exhibited higher immunoreactivity for cleaved (activated) caspase-8 than poor prognosis tumors. CONCLUSIONS: In thyroid carcinomas, the proteolytic cleavage and activation of caspase-8 depends on the balance between expression levels for procaspase-8 and FLIP and correlates with favorable clinical prognosis. Fas may actually stimulate proliferation and confer a survival advantage to thyroid cancer cells. Notes:
	DOI PMID Sofia Tseleni-Balafouta, Hariklia Gakiopoulou, Galinos Fanourakis, Gerassimos Voutsinas, Helen Litsiou, Elias Sozopoulos, Dimitrios Balafoutas, Efstratios Patsouris (2006) Fibrillin expression and localization in various types of carcinomas of the thyroid gland. Mod Pathol 19: 5. 695-700 May Abstract: Fibrillin is an extracellular matrix (ECM) glycoprotein, a main component of microfibrills, suggested to support cell attachment and to impact cell differentiation and migration. The aim of this study was to investigate fibrillin-1 expression in thyroid carcinomas at mRNA and protein level, since ECM proteins are suggested to be of great importance for the metastatic potential of carcinomas. RNA was extracted from 13 thyroid carcinoma cell lines and RT-PCR analysis with gene-specific primers revealed fibrillin-1 mRNA expression in all cell lines, with highest expression in the follicular carcinoma cell line WRO and lowest expression in the two anaplastic cell lines (APO, FRO). Furthermore, we investigated fibrillin-1 expression by immumohistochemistry in a commercially available tissue microarray including 50 thyroid carcinomas as well as in archival tissue from 33 thyroid carcinomas. Fibrillin-1 demonstrated a cytoplasmic location in the neoplastic cells of almost all carcinomas apart from the follicular ones. The most intense staining was observed in papillary carcinomas with some evidence of a slight increased intensity in advanced stages. Our data indicate that fibrillin-1 is strongly expressed by the neoplastic cells of thyroid carcinomas in different degree in the various histologic types and might be implicated in cell-stroma interaction in terms of signaling, attachment and migration. Notes:
2005	DOI PMID Vassiliki Poulaki, Constantine S Mitsiades, Ciaran McMullan, Galinos Fanourakis, Joseph Negri, Athina Goudopoulou, Ioannis X Halikias, Gerassimos Voutsinas, Sophia Tseleni-Balafouta, Joan W Miller, Nicholas Mitsiades (2005) Human retinoblastoma cells are resistant to apoptosis induced by death receptors: role of caspase-8 gene silencing. Invest Ophthalmol Vis Sci 46: 1. 358-366 Jan Abstract: PURPOSE: Fas ligand (FasL) and TNF-related apoptosis-inducing ligand (TRAIL)/Apo2L are members of the TNFalpha family that can trigger apoptosis in susceptible cells via respective death receptors (DRs). FasL cross-links its receptor Fas, resulting in recruitment and proteolytic activation of caspase-8, which initiates the downstream apoptotic cascade. TRAIL signals through its receptors DR4 and DR5, which can activate caspase-8 as well. This study was undertaken to investigate the functional status of the FasL and TRAIL apoptotic pathways in retinoblastoma (Rb) cells. METHODS: The human Rb cell lines Y79 and WERI-Rb1 were evaluated for their response to the Fas cross-linking antibody CH11 and recombinant TRAIL, as well as for cell surface presence and mutational status of Fas, DR4, and DR5 by flow cytometry and genomic DNA sequencing, respectively. The expression of caspase-8 and its inhibitor FLIP, as well as their recruitment to the DR signaling complex were studied by immunoblot analysis. RESULTS: Rb cells express Fas, DR4, and DR5 on their surfaces, yet were resistant to DR-mediated apoptosis. This was not due to DR mutations or secretion of the soluble decoy Fas, antiapoptotic NF-kappaB activity, or FLIP overexpression, but to the absence of caspase-8 expression. The demethylating agent 5-aza-2'-deoxycytidine restored caspase-8 expression and sensitivity to DR-mediated apoptosis. CONCLUSIONS: Rb cells are resistant to DR-mediated apoptosis because of a deficiency in caspase-8 expression secondary to epigenetic gene silencing by overmethylation. The data help delineate the apoptotic pathways in Rb cells and suggest that the combination of demethylating agents with DR-activating modalities, such as TRAIL receptor monoclonal antibodies, may benefit patients with retinoblastoma. Notes:

2004	DOI PMID Penelope Korkolopoulou, Athina Goudopoulou, Gerassimos Voutsinas, Euphemia Thomas-Tsagli, Panagiotis Kapralos, Efstratios Patsouris, Angelica A Saetta (2004) c-FLIP expression in bladder urothelial carcinomas: its role in resistance to Fas-mediated apoptosis and clinicopathologic correlations. Urology 63: 6. 1198-1204 Jun Abstract: OBJECTIVES: To investigate the incidence of Fas (exon 9) mutations and the expression of Fas, Fas-Fas ligand (FasL) system, and cellular FLICE-like inhibitory protein (c-FLIP) in relation to standard clinicopathologic parameters and patient outcome in bladder carcinoma. Disruption of apoptotic cell death has been implicated in tumor aggressiveness in bladder urothelial carcinomas. The FasL system is involved in the execution of apoptosis induced by the immune system. c-FLIP protein constitutes an important endogenous inhibitor of Fas and other death receptor-mediated apoptosis. METHODS: The expression of Fas, FasL, and c-FLIP was quantified immunohistochemically in paraffin-embedded tissues from 53 patients for whom clinical information was available. DNA extracted from the same samples was screened for mutations in Fas exon 9 by single-strand conformation polymorphism and sequencing. The effect of Fas, FasL, and c-FLIP on clinical outcome was assessed by univariate and multivariate analyses. RESULTS: Positive immunostaining was detected for Fas, FasL, and c-FLIP in 72%, 66%, and 81% of cases, respectively. Concurrent expression of Fas and FasL was seen in 27 samples (51%), of which 22 (81.5%) also displayed c-FLIP positivity. FasL and c-FLIP expression increased with advancing stage but was absent from normal urothelium. None of the 53 urothelial carcinoma samples analyzed showed evidence of mutations by polymerase chain reaction single-strand conformation polymorphism and direct sequencing. Survival analysis demonstrated that although both FasL and c-FLIP expression adversely affected survival, only c-FLIP remained statistically significant on multivariate analysis. CONCLUSIONS: The frequent expression and coexpression of Fas, FasL, and c-FLIP in urothelial carcinomas implicates c-FLIP as an inhibitor of the Fas-FasL-induced death pathway in these tumors. Moreover, c-FLIP conveys independent prognostic information in the presence of classical prognosticators. Notes:
	DOI PMID Panagiotis G Bakas, Angelos E Liapis, Irene Zervolea, Georgios Voutsinas, Demetrios Kletsas, Georgios Creatsas (2004) mRNA assessment for procollagen production in women with genuine stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 15: 6. 429-31; discussion 431 Nov/Dec Abstract: The aim of the study was to examine changes in the levels of mRNA for procollagen type I and III in women with or without genuine stress incontinence (GSI). The study was performed in the 2nd Department of Obstetrics and Gynecology of University of Athens. Sixty-eight women participated in the study and they were divided in two groups. We did not find statistically significant difference between the two groups of patients in relation to the amount of mRNA of procollagen type I and III (p>0.05), but the quantity of collagen type I and III was significantly reduced in patients with stress incontinence (p<0.05). The possible cause for the reduction in the amount of collagen in women with GSI could be attributed to either a disturbance in the translation of mRNA to protein (collagen) or increased catabolism of collagen by its collagenase. Notes:
	DOI PMID A A Saetta, A Goudopoulou, P Korkolopoulou, G Voutsinas, E Thomas-Tsagli, N V Michalopoulos, E Patsouris (2004) Mononucleotide markers of microsatellite instability in carcinomas of the urinary bladder. Eur J Surg Oncol 30: 7. 796-803 Sep Abstract: AIMS: To determine the presence of microsatellite instability (MSI) and to assess the expression of the human mismatch repair (MMR) gene products hMLH1 and hMSH2 in primary transitional cell carcinomas (TCCs) of the urinary bladder in relation to clinico-pathological parameters. METHODS: Seventy-two cases of primary TCC were screened for the presence of alterations in MSI markers by molecular techniques and evaluated immunohistochemically for the expression of hMLH1 and hMSH2 proteins. Clinical data were available in 70 cases. The percentage of MSI rose to 16.6%. RESULTS: Reduced (<20%) hMLH1 expression was closely related to the presence of MSI (p=0.0004). Neither MMR proteins nor MSI was associated with grade, stage, papillary status. Clinical outcome analysed as a function of MSI did not show significant differences in terms of both disease-free and overall survival. Reduced hMLH1 expression was a significant predictor of shorter disease-free survival in univariate and multivariate analysis. CONCLUSIONS: The presence of MSI is not related to classical clinico-pathological parameters in TCCs, nor does it appear to be of prognostic significance. hMLH1 was an important indicator for recurrence. Notes:
2003	PMID Nikolaos V Michalopoulos, Angelica Saetta, Andreas Ch Lazaris, Gerassimos Voutsinas, Panayiotis S Davaris (2003) Detection of genetic abnormalities in neoplasms from Greek patients with FAP. Eur J Surg Oncol 29: 1. 38-43 Feb Abstract: AIMS: DNA microsatellite instability is a well-known feature of hereditary non-polyposis colon cancer; however, its incidence in familial adenomatous polyposis, is unclear. We report the frequency of microsatellite instability and other genetic abnormalities in a group of Greek patients with FAP, in relation to various clinicopathological variables. METHODS: Thirty-four tissue specimens from 10 patients with FAP were studied. Microsatellite instability was investigated at six loci: BAT25, BAT26, D2S123, D5S346, D17S250 and TGF-beta RII poly(A) tract. p53 and K-ras mutations were also examined. RESULTS: Microsatellite instability was detected in two FAP adenocarcinomas from different patients. Mutation percentages observed were: in K-ras 45% and 50% and in p53 14% and 58%, of FAP adenomas and adenocarcinomas, respectively. No K-ras or p53 mutations were determined in the two microsatellite instable adenocarcinomas. CONCLUSION: Microsatellite instability is detectable in a small proportion of adenocarcinomas complicating FAP. This minority of cases may constitute a distinct subgroup among FAP neoplasms. Notes:
	PMID Liliana Puiu, Eftichia Petrakou, Anastasia Apostolidou, Aglaia Athanassiadou, Lambrini Psiouri, Adamantia Papachatzopoulou, Vassilis G Gorgoulis, Athanassios Kotsinas, Evangelos Tzoracoeleftherakis, George M Maniatis, Gerassimos Voutsinas (2003) Lack of Fas (APO-1/CD95) gene structural alterations or transcript variant ratio changes in breast cancer. Cancer Lett 194: 1. 91-97 May Abstract: Fas (APO-1/CD95) is a transmembrane receptor protein involved in cell death signaling. Fas receptor and ligand are both expressed in breast cancer cells, however these cells are resistant to apoptosis. Fas gene mutations were detected in hematological and solid tumors, while overexpression of a soluble Fas isoform in serum was related to cancer stage and prognosis. In this work, direct sequencing of exons 6 and 9 of the Fas gene from 90 patients did not reveal any structural alterations. Moreover, no decrease was found in the ratio of the corresponding mRNA species of transmembrane versus soluble Fas isoforms in 31 breast cancer samples compared to 14 controls. Therefore, inhibition of Fas-mediated apoptosis may not be due to structural alterations in the critical exons 6 and 9 of the Fas gene or a shift of expression towards the soluble Fas isoform, but to other mechanisms operating in breast cancer cells. Notes:
2001	PMID G Voutsinas (2001) Mutagenesis, apoptosis, basic relation to carcinogenic models. Folia Histochem Cytobiol 39 Suppl 2: 56-57 Abstract: Cancer arises from an accumulation of mutations as well as changes in the expression pattern of genes mainly involved in cell cycle regulation, DNA repair and apoptosis, which promote clonal selection of cells with an increasingly malignant phenotype. Although a single mutant gene may not be able to redirect the growth program of a normal cell, the multiplicity of downstream targets of a deregulated molecule and the extensive cross-talk between biochemical pathways suggest that cellular context and genotype are of great importance in cancer initiation, while gene activation and inactivation events may not be independent. Complex exposure patterns affecting molecular targets exhibiting multiple intracellular interactions add a significant percentage of uncertainty when assessing cancer risk. Notes:
1999	DOI PMID A Athanassiadou, G Voutsinas, L Psiouri, E Leroy, M H Polymeropoulos, A Ilias, G M Maniatis, T Papapetropoulos (1999) Genetic analysis of families with Parkinson disease that carry the Ala53Thr mutation in the gene encoding alpha-synuclein. Am J Hum Genet 65: 2. 555-558 Aug Abstract: Notes:
	DOI PMID T Timmer, P Terpstra, A van den Berg, P M Veldhuis, A Ter Elst, G Voutsinas, M M Hulsbeek, T G Draaijers, M W Looman, K Kok, S L Naylor, C H Buys (1999) A comparison of genomic structures and expression patterns of two closely related flanking genes in a critical lung cancer region at 3p21.3. Eur J Hum Genet 7: 4. 478-486 May/Jun Abstract: In the search for a tumour suppressor gene in the 3p21.3 region we isolated two genes, RBM5 and RBM6. Gene RBM5 maps to the region which is homozygously deleted in the small cell lung cancer cell line GLC20; RBM6 crosses the telomeric breakpoint of this deletion. Sequence comparison revealed that at the amino acid level both genes show 30% identity. They contain two zinc finger motifs, a bipartite nuclear signal and two RNA binding motifs, suggesting that the proteins for which RBM5 and RBM6 are coding have a DNA/RNA binding function and are located in the nucleus. Northern and Southern analysis did not reveal any abnormalities. By SSCP analysis of 16 lung cancer cell lines we found only in RBM5 a single presumably neutral mutation. By RT-PCR we demonstrated the existence of two alternative splice variants of RBM6, one including and one excluding exon 5, in both normal lung tissue and lung cancer cell lines. Exclusion of exon 5 results in a frameshift which would cause a truncated protein of 520 amino acids instead of 1123 amino acids. In normal lung tissue, the relative amount of the shorter transcript was much greater than that in the lung tumour cell lines, which raises the question whether some tumour suppressor function may be attributed to the derived shorter protein. Notes:
1998	PMID R Vachkova, A Kappas, E Tyagunenko, M Markaki, G Voutsinas (1998) Specific recombinogenic activity of a new polyene antibiotic. Cell Mol Life Sci 54: 2. 143-147 Feb Abstract: A new antibiotic from Streptomyces sp., tetrapol A159, active against various fungi, a promising compound for the control of plant diseases, was studied for its genotoxic effects. It was produced at the Institute of Microbiological Preparations for Agriculture, Sofia, Bulgaria. The chemical was tested in three different test systems: a bacterial system, the Ames test for point mutations, the micronucleus test in bone marrow cells of rats for chromosomal aberrations and the fungal system of Aspergillus nidulans for mitotic recombination and aneuploidy. No increase in histidine revertants was observed in any of the TA100, TA98, TA1535 and TA1537 strains of Salmonella at concentrations ranging from 1 to 4000 mg/plate. The results were also negative in the micronucleus test of bone marrow cells at concentrations from 124 to 600 mg/kg b.w., whereas a statistically significant threefold increase of mitotic crossovers was found in Aspergillus, at concentrations from 0.5 to 2.5 mg/ml. Notes:
1997	DOI PMID G Voutsinas, F E Zarani, A Kappas (1997) The effect of environmental aneuploidy-inducing agents on the microtubule architecture of mitotic meristematic root cells in Hordeum vulgare. Cell Biol Int 21: 7. 411-418 Jul Abstract: Microtubules are the prime components involved in chromosomal segregation, their functional accuracy ensuring maintenance of the normal karyotype in the progeny. Chemically-induced disruption of microtubules during mitosis can lead to aneuploidy. In this study, seven environmental chemicals, i.e. cadmium chloride (CD), econazole nitrate (EZ), benomyl (BM), thiabendazole (TB), griseofulvin (GF), thimerosal (TM) and hydroquinone (HQ), were tested for their ability to induce microtubule disruption in mitotic meristematic root cells of the higher plant Hordeum vulgare, with the use of anti-tubulin indirect immunofluorescence microscopy. All chemicals tested in this study, with the exception of TB and HQ, produced modifications in the morphology of microtubule organization and reduced the fidelity of the spindle apparatus in Hordeum vulgare. Notes:
1994	PMID T Gichner, G Voutsinas, A Patrineli, A Kappas, M J Plewa (1994) Antimutagenicity of three isomers of aminobenzoic acid in Salmonella typhimurium. Mutat Res 309: 2. 201-210 Sep Abstract: The m-, o- and p-isomers of aminobenzoic acid (ABA) repressed the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Salmonella typhimurium TA100. Their antimutagenic potency was in the order of o-ABA > m-ABA > p-ABA. The mechanism of this antimutagenicity is ascribed mainly to the decomposition of MNNG induced by the aminobenzoic acid isomers outside or within the bacterial cells. The inhibition of plant cell peroxidases and bacterial acetyltransferases that are required for the plant activation of 2-aminofluorene (2-AF) to mutagenic product(s) may participate in the repression of 2-AF mutagenesis by the aminobenzoic acids in S. typhimurium strain YG1024. The aminobenzoic acid isomers exhibited no inhibitory effects towards the direct-acting agent 2-acetoxy-2-acetylaminofluorene, the stable diacetylated metabolic product of 2-AF. Notes:
1993	PMID G Voutsinas, A Kappas, N A Demopoulos, C Camoutsis (1993) Mutagenicity of four homo-aza-steroidal esters of m-N,N-bis(2-chloroethyl)aminocinnamic acid in the Ames test. Mutat Res 319: 4. 325-329 Dec Abstract: Four new chemicals, the homo-aza-steroidal esters of m-N,N-bis(2-chloroethyl)aminocinnamic acid, originaly synthesized to be used as antineoplastic agents, were tested for their mutagenic activity in the Ames test. 3 beta-Hydroxy-13 alpha-amino-13,17-seco-5-androsten-17-oic-13,17- lactam ester (ACALE3) and 3 alpha-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam ester of m-N,N-bis(2-chloroethyl)aminocinnamic acid (ACALE4) were found to induce base-pair substitutions, causing dose-dependent increases in his+ revertants in strains TA100 and TA1535, while no dose-dependent relations were established when 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam ester (ACALE1) and 17 beta-hydroxy-3-aza-A-homo-4 alpha-androsten-4-one ester of m-N,N-bis(2-chloroethyl)aminocinnamic acid (ACALE2) were tested. The presence of metabolic activation enzymes in the test system had no effect in his+ revertants in strains TA100 and TA1535. The chemicals tested although having the same alkylating moiety and a similar chemical structure exhibited different mutagenic activities. Notes:
	PMID G Voutsinas, A Kappas, N A Demopoulos, P Catsoulacos (1993) Mutagenic activity of the antitumour agent homo-aza-steroidal ester of p-N,N-bis(2-chloroethyl)aminophenoxyacetic acid (NSC 294859) in the Salmonella/microsome assay. Mutagenesis 8: 5. 431-435 Sep Abstract: The mutagenic activity of the new antitumour agent 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam- p-N,N-bis(2-chloroethyl)aminophenoxyacetate (NSC 294859) was studied in the Salmonella/microsome assay. It was found to induce base pair substitutions, causing dose-dependent increases in his+ revertants in strains TA100 and TA1535. The alkylating moiety, p-N,N-bis(2-chloroethyl)-aminophenoxyacetic acid, was shown to be less effective than the parent compound, while the modified steroid moiety, 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam, showed no mutagenic effect in all strains used. The presence of metabolic activation enzymes in the test system induced a further increase in his+ revertants in strains TA100 and TA1535, in both the parent compound and the alkylating moiety of the parent compound, while it had no effect in the case of the steroidal lactam. Notes:
	PMID G Voutsinas, A Kappas, N A Demopoulos, P Catsoulacos (1993) Comparative study on the mutagenicity of three structurally related substituted aniline mustards in the Salmonella/microsome assay. Mutat Res 298: 4. 261-267 Feb Abstract: The ortho, meta and para isomers of N,N-bis(2-chloroethyl)aminocinnamic acid were tested for their ability to mutate Salmonella typhimurium strains in the Salmonella/microsome mutagenicity test. The aim of the work was to establish a structure-activity relationship between these three isomers. The drugs were found to induce base-pair substitutions, causing dose-dependent increases in his+ revertants, in strains TA100 and TA1535. The study showed that the position of the substituent groups influenced the mutagenic activity of the compounds. The ortho isomer exhibited a poorer mutagenic effect than meta and this was found to be a weaker mutagen than para. The presence of metabolic activation enzymes in the test system induced a further increase in his+ revertants, in strains TA100 and TA1535, which is consistent with the findings for melphalan, a cancer chemotherapeutic agent with a chemical structure similar to that of the isomers tested. Notes:

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