Department of Molecular Biology of Cancer

Department of Molecular Biology of Cancer

Department of the Molecular Biology of Cancer

 

 
 

Head: Pavel Vodička, MD, PhD.

Tel.: +420 241 062 694

 

In our Department we investigate molecular characteristics of solid cancers, especially of the colon, rectum, pancreas and ovaries. Within these studies we focus on the molecular epidemiological level in order 1. to identify biomarkers of increased predisposition to tumour diseases, 2. enable early diagnostics, 3. assess individual responses to anti-tumour treatment, 4. and determine long-term prognosis. We focus mainly on the system of DNA damage repair. This extensive biological process is ensured by a minimum of six more or less independent pathways and is of a crucial importance for maintaining the structural and functional stability of DNA and thus ensures the prevention of neoplastic transformation of healthy cells. On the other hand, the activity of DNA damage repair is significantly applied also during the response of tumour cells to the impact of chemotherapeutics. The treatment by some of the most commonly used drugs proceeds via massive DNA damage and subsequent cell death. High activity of DNA repair mechanisms may contribute to resistance of cancer cells to such substances. The Department has been working with different types of biological material from a patients with cancer diseases, such as solid tissue, blood cells or plasma.

 

 

 
Research Scientists:
Pavel Vodička, MD, PhD.
Alena Opattová, PhD.
Jana Slyšková, PhD.
Ludmila Vodičková, MD, PhD.
Markéta Urbanová, MSc, PhD.
Veronika Poláková-Vymetálková, MSc, PhD.
 
 
PhD Students:
Linda Bártů, MSc
Petra Bendová, MSc
Andrea Čumová, MSc
Kateřina Jirásková, MSc
Jan Král, MD
Michal Kroupa, MSc
Alexandra Rejhová, MSc
Soňa Vodénková, MSc
 
Undergraduate Students:
Klára Červená
 
External Collaborators:
Pavel Kříž
Prof. Rudolf Štětina, PhD.

 

Important results in 2015

 

1. Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects
Numerical and structural chromosomal instability takes part in carcinogenesis. We studied functional variants in DNA repair genes in relation to chromosomal damage (CA), chromatid-type (CTA) and chromosome-type aberrations (CSA) in healthy subjects. We found significantly lower CTA frequencies associated with XPD Lys751Gln variant genotype and increased CSA linked to the RAD54L variant genotype. CAs accumulation requires complex interplay between different DNA repair pathways.

 

The genesis of DNA and chromosomal damage in human DNA
Many exogenous agents attack DNA and generate single-and double-strand breaks. If not repaired by DNA repair mechanisms, they may result in permanent chromosomal damage and ultimately in the onset of cancer.

 

 

 

Publication:
Vodička, P., Musak, L., Frank, C., Kazimirova, A., Vymetálková, V., Barancoková, M., Smolková, B., Dzupinková, Z., Jirasková, K., Vodenková, S., Kroupa, M., Osina, O., Naccarati, A., Palitti, F., Försti, A., Dusinská, M., Vodičková, L., Hemminki, K.: (2015) Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects. Carcinogenesis.36(11): 1299-1306. IF 5.334

 

2. Post-Treatment Recovery of Suboptimal DNA Repair Capacity and Gene Expression Levels in Colorectal Cancer Patients
We studied the dynamics of DNA repair in colorectal cancer patients from diagnosis to 1yr follow up, and with respect to CRC treatment. We identified a panel of blood DNA repair-related markers discerning acute stage of the disease from the remission period. In conclusion, our results support a model in which DNA repair is altered as a result of cancer.

Commet assay shows the extent of DNA damage and repair. Undamaged DNA is supposed to be compact in nucleus, damaged DNA appears as a tail of fluorescence.

  

Publication:
MOLECULAR CARCINOGENESIS 54:769–778 (2015); Jana Slyskova, Francesca Cordero, Barbara Pardini, Vlasta Korenkova, Veronika Vymetalkova, Ludovit Bielik, Ludmila Vodickova, Pavel Pitule, Vaclav Liska, Vit Martin Matejka, Miroslav Levy, Tomas Buchler, Mikael Kubista, Alessio Naccarati, and Pavel Vodicka

 

3. Polymorphisms in microRNA genes as predictors of clinical outcomes in colorectal cancer patients
Colorectal cancer (CRC) is routinely cured by a 5-fluorouracil (5-FU)-based chemotherapy. We investigated the effect of single nucleotide polymorphisms in two microRNA - encoding genes in 1083 CRC patients recruited in the Czech Republic and we evaluated effect of 5FU therapy on clinical outcomes. Obtained results confirm that variations in miRNA-encoding genes may be an important factor modulating CRC prognosis and predicting therapy response.

 

Kaplan–Meier EFS curves stratified (A) for rs213210 in all CRC patients undergoing 5-FU-based chemotherapy, and (B) for rs4919510 in stage III CRC patients undergoing 5-FU-based chemotherapy. MST, median survival time.

 

Publication:
Carcinogenesis vol.36 no.1 pp.82–86, 2015; BarbaraPardini, Fabio Rosa, Alessio Naccarati, Veronika Vymetalkova, Yuanqing Ye, Xifeng Wu, Cornelia di Gaetano, Tomas Buchler, Jan Novotny, Giuseppe Matullo and Pavel Vodicka

 

Important results in 2014



1. Susceptibility loci in pancreatic cancer
We have for the first time identified four new susceptibility loci, affecting the risk to pancreatic cancer. Simultaneously the relationship between pancreatic cancer and vartiants in exon 2 in TERT and telomeric PVT1 were proven. Our results add to the evidence for multifactorial pathogenesis of pancreatic cancer, which represents one of the most dreadful malignancies. Our findings contribute to understand the cause and development of the disease and to design effective therapeutical strategy.

 

 

Publication:

Wolpin BM, Rizzato C, Kraft P, Kooperberg C, Petersen GM, Wang Z, Arslan AA, Beane-Freeman L, Bracci PM, Buring J, Canzian F, Duell EJ, Gallinger S, Giles GG, Goodman GE, Goodman PJ, Jacobs EJ, Kamineni A, Klein AP, Kolonel LN, Kulke MH, Li D, Malats N, Olson SH, Risch HA, Sesso HD, Visvanathan K, White E, Zheng W, Abnet CC, Albanes D, Andriotti G, Austin MA, Barfi eld R, Basso D, Berndt SI, Boutron-Ruault MC, Brotzman M, Buchler MW, Bas Buenode-Mesquita H, Bugert P, Burdette L, Campa D, Caporaso NE, Capurso G, Chung C, Cotterchio M, Costello E, Elena J, Funel N, Gaziano M, Giese N, Giovannucci EL, Goggins M, Gorman MJ, Gross M, Haiman C, Hassan M, Helzlsouer K, Henderson BE, Holly EA, Hu N, Hunter DJ, Innocenti F, jenab M, Kaaks R, Key TJ, Khaw KT, Klein EA, Kogevinas M, Kupcinskas J, Kurtz RC, LaCroix A, Landi MT, Landi S, Le Marchand L, Mambrini A, Mannisto S, Milne RL, Nakamura Y, Oberg AL, Owzar K, Panico S, Patel AV, Peeters PH, Peters U, Piepoli A, Porta M, Real FX, Riboli E, Rothman N, Scarpa A, Shu X, Silverman DT, Soucek P, Sund M, Talar-Wojnarowska R, Taylor PR, Theodoropoulos GE, Thornquist M, Tjoenneland A, Tobias GS, Trichopoulos D, Vodička P, Wactawski-Wende J, Wentzensen N, Wu C, Yu H, Yu K, Zeleniuch-Jacquotte A, Hoover R, Hartge P, Fuchs C, Channock S, Stolzenberg-Solomon RS, Amundadottir L (2014): Genome-wide association study identifi es multiple susceptibility loci for pancreatic cancer. Nature Genet. 46(9):994-1000. IF: 29.648

 

 

2. Genetic and epigenetic factors affecting colorectal cancer
In the studies shown below we addressed the effects of gene variants, miRNA binding sites and epigenetic regulatory mechanisms on the onset, prognosis and effective therapy of colorectal cancer.

 

 

Survival analysis of patients with low and high levels of long-non-coding-RNA.

 

Collaboration: DKFZ Heidelberg, FRG, HUGE Turin, Italy, University in Umea, Sweden etc.

 

Publications:

Lu S, Pardini B, Cheng B, Naccarati A, Huhn S, Vymetálková V, Vodičková L, Buchler T, Hemminki K, Vodicka P, Försti A. (2014) Single Nucleotide Polymorphisms within Interferon Signaling Pathway Genes Are Associated with Colorectal Cancer Susceptibility and Survival. PLoS One 9(10): e111061. IF 3.534

Huhn S, Bevier M, Pardini B, Naccarati A, Vodickova L, Novotny J, Vodicka P, Hemminki K, Försti A. Colorectal cancer risk and patients' survival: influence of polymorphisms in genes somatically mutated in colorectal tumors. Cancer Causes Control. 2014 Jun;25(6):759-69. IF: 2.961

Vymetalkova V, Pardini B, Rosa F, Di Gaetano C, Novotny J, Levy M, Buchler T, Slyskova J, Vodickova L, Naccarati A, Vodicka P. Variations in mismatch repair genes and colorectal cancer risk and clinical outcome. Mutagenesis 2014 Jul;29(4):259-65. IF: 3.495

Vymetalkova Polakova V, Slyskova J, Korenkova V, Bielik L, Langerova L, Prochazka P, Rejhova A, Schwarzova L, Pardini B, Naccarati A, Vodicka P. Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients. BMC Medical Genetics 2014. IF: 2.450

Farkas S, Vymetalkova V, Vodickova L, Vodicka P, Nilsson TK. DNA methylation changes in genes frequently mutated in colorectal cancer and in the DNA repair and Wnt/β-catenin signaling pathway genes. Epigenomics 2014 Apr;6(2):179-91. IF: 5.215

Svoboda M, Slyskova J, Schneiderova M, Makovicky P, Bielik L, Levy M, Lipska L, Hemmelova B, Kala Z, Protivankova M, Vycital O, Liska V, Schwarzova L, Vodickova L, Vodicka P. HOTAIR long non-coding RNA is a negative prognostic factor not only in primary tumors, but also in the blood of colorectal cancer patients. Carcinogenesis. 2014 Jul;35(7):1510-5. IF: 5.266
 

 

3. Mapping of DNA repair capacities
Important data have been obtained by studying DNA repair mechanisms and the genomic integrity. DNA repair capacity has been mapped in healthy subjects as well as in colorectal cancer patients, with emphasis to the prognosis and therapy. We have for the fi rst time proven the relationship between genetic variants in cyclin D1 and DNA damage response, homologous recombination repair process and chromosomal damage.

 

 

Schematic outline of factors influencing nucleotide excision repair (NER) – DNA repair capacity (DRC) phenotype.

 

Collaboration: University of Oslo, Norway, DKFZ heidelberg, FRG, HUGE Turin, Italy etc.

Publications:

Slyskova J, Langie SA, Collins AR, Vodicka P. Functional evaluation of DNA repair in human biopsies and their relation to other cellular biomarkers. Front Genet. 2014 May 23;5:116. doi: 10.3389/fgene.2014.00116. eCollection 2014.

Slyskova J, Lorenzo Y, Karlsen A, Carlsen M, Novosadova V, Blomhoff R, Vodicka P, Collins AR. Both genetic and dietary factors underlie differences in DNA damage levels and DNA repair capacity. DNA Repair 16 (2014) 66–73. IF: 3.362

Slyskova J, Cordero F, Pardini B, Korenkova V, Vymetalkova V, Bielik L, Vodickova L, Pitule P, Liska V, Matejka VM, Levy M, Buchler T, Kubista M, Naccarati A, Vodicka P. Post-treatment recovery of suboptimal DNA repair capacity and gene expression levels in colorectal cancer patients. Mol Carcinog. 2014 Mar 3. doi: 10.1002/mc.22141. [Epub ahead of print] PubMed PMID: 24585457. IF: 4.770

Hemminki K, Musak L, Vymetalkova V, Smerhovsky Z, Halasova E, Osina O, Letkova L, Försti A, Vodickova L, Buchancova J, Vodicka P. Cyclin D1 splice site variant triggers chromosomal aberrations in healthy humans. Leukemia. 2014 Mar;28(3):721-2. IF: 9.379

 

 

Important results in 2013



1. We have published a comprehensive protocol of techniques for evaluation of activity of two DNA repair pathways – base and nucleotide excision repair – and their application on different types of biological material.

 

 

Scheme of the comet based assay to measure DNA repair

 

Publication: 
Azqueta, A., Langie, S. A., Slyskova, J., Collins, A. R.: (2013) Measurement of DNA base and nucleotide excision repair activities in mammalian cells and tissues using the comet assay - A methodological overview. DNA Repair (Amst). 12:1007-1010. IF 4,274
 

 

2. We have shown that there is a relationship between colorectal cancer patients‘ response to therapy with 5-fluorouracil and their overall survival and genetic polymorphism in DNA repair gene, located in the microRNA binding site. This polymorphism, after the verification by independent study, may represent a predictive and prognostic marker in colorectal cancer.

 

Kaplan-Meier curve showing relationship between overal survival and genetic variant rs2233921 in SMUG1 in colorectal cancer patients.

 

Publication: 
Pardini B., Rosa F., Barone E., Di Gaetano C., Slyskova J., Novotny J., Levy M., Garritano S., Vodickova L., Buchler T., Gemignani F., Landi S., Vodicka P., Naccarati A.: (2013) Variation within 3‘ UTRs of base excision repair genes and response to therapy in colorectal cancer patients: a potential modulation of microRNAs binding. Clin Cancer Res. 12(21): 6044-56. IF 7,837

GACR, P301/12/1734, Analysis of role of genetic factors in pancreatic cancer risk and prognosis. (2012-2016), EB, PI Dr. Souček, SZU

GACR, P304/12/1585, Molecular characteristics of DNA repair in colorectal tumor tissue. (2012 – 2015) EB, PI: Dr. Vodička, 1.LF UK

GACR, P304/15/08239S The diagnostic, predictive and prognostic role of microRNA signature in rectal cancer (2015-2017), EB. PI: Slyšková, ÚEM

GACR, P303/15/14789S Stress response to DNA damage in colorectal carcinogenesis. (2015-2017) EB, PI: Dr. Vodička, ÚEM

IGA MZCR NT-13424, MiR137 and its influence on the production of mucin as a potential tool in early diagnosis of colorectal cancer or colorectal cancer relapse. (1.4.2012-2015)FJ, PI: Dr. Levý, Thomayerova nemocnice.

IGA MZCR NT 14329-3/2013, Evaluation of molecular and biological factors for prognosis of generalisation of surgicaly treated colorectalcancer. (1.5.2013-2015), PI: Dr. Liška, LF Plzeň

IGA MZCR NT 14056-3/2013, Molecular and genetic biomarkers in pathogenesis and resistency in ovarian carcinoma.(1.5.2013-2015), PI: Dr. Václavíková, SZÚ

Bilateral czech-american project MSMT, LH 13061: Role of Ganoderma Lucidum Extracts in the Regulation of NFkB- DNA Repair-Proteasome Interactions in colorectal carcinogenesis. (2013-2015), PI: Dr. Vodička, ÚEM

SUSCEPTCOST MSMT LD14050 Genetic and functional determinants of colorectal tumors; outcomes for individualized therapy (4/2014-4/2017).

AZV 15-27580A Taste perception, oxidative damage and colon microenvironment in colorectal carcinogenesis: impacts on the disease risk, prognosis and prevention (5/2015-2019); PI: Dr. Vodička, (1.5.2015-2019).

AZV 15-26535A (5/2015-2018) The role of genetic variations in microRNA genes and in microRNA binding sites in colorectal cancer in relation to personalized therapy. PI: Ing. Vymetálková, (1.5.2015-2019).

2016

Naccarati, A., Rosa, F., Vymetálková V., Barone, E., Jirásková, K., Di Gaetano, C., Novotný, J., Levy, M., Vodičková, L., Gemignani, F., Buchler, T., Landi, S., Vodička, P., Pardini, B.: (2016) Double-strand break repair and colorectal cancer: gene variants within 3' UTRs and microRNAs binding as modulators of cancer risk and clinical outcome. Oncotarget, IN PRESS

 

2015

Aherne, S.T., Madden, S.F., Hughes, D.J., Pardini, B., Naccarati, A., Levy, M., Vodička, P., Neary, P., Dowling, P., Clynes, M.: (2015) Circulating miRNAs miR-34a and miR-150 associated with colorectal cancer progression. BMC Cancer. 15: 329.

Campa, D., Rizzato, C., Stolzenberg-Solomon, R., Pacetti, P., Vodička, P., Cleary, S.P., Capurso, G., Bueno-de-Mesquita, H.B., Werner, J., Gazouli, M., Butterbach, K., Ivanauskas, A., Giese, N., Petersen, G.M., Fogar, P., Wang, Z., Bassi, C., Ryska, M., Theodoropoulos, G.E., Kooperberg, C., Li, D., Greenhalf, W., Pasquali, C., Hackert, T., Fuchs, C.S., Mohelnikova-Duchonova, B., Sperti, C., Funel, N., Dieffenbach, A.K., Wareham, N.J., Buring, J., Holcátová, I., Costello, E., Zambon, C.F., Kupcinskas, J., Risch, H.A., Kraft, P., Bracci, P.M., Pezzilli, R., Olson, S.H., Sesso, H.D., Hartge, P., Strobel, O., Małecka-Panas, E., Visvanathan, K., Arslan, A.A., Pedrazzoli, S., Souček, P., Gioffreda, D., Key, T.J., Talar-Wojnarowská, R., Scarpa, A., Mambrini, A., Jacobs, E.J., Jamroziak, K., Klein, A., Tavano, F., Bambi, F., Landi, S., Austin, M.A., Vodičková, L., Brenner, H., Chanock, S.J., Delle Fave, G., Piepoli, A., Cantore, M., Zheng, W., Wolpin, B.M., Amundadottir, L.T., Canzian, F.: (2015) TERT gene harbors multiple variants associated with pancreatic cancer susceptibility. Int J Cancer. 1;137(9):2175-2183.

Childs, E.J., Mocci, E., Campa, D., Bracci, P.M., Gallinger, S., Goggins, M., Li, D., Neale, R.E., Olson, S.H., Scelo, G., Amundadottir, L.T., Bamlet, W.R., Bijlsma, M.F., Blackford, A., Borges, M., Brennan, P., Brenner, H., Bueno-de-Mesquita, H.B., Canzian, F., Capurso, G., Cavestro, G.M., Chaffee, K.G., Chanock, S.J., Cleary, S.P., Cotterchio, M., Foretová, L., Fuchs, C., Funel, N., Gazouli, M., Hassan, M., Herman, J.M., Holcatová, I., Holly, E.A., Hoover, R.N., Hung, R.J., Janout, V., Key, T.J., Kupcinskas, J., Kurtz, R.C., Landi, S., Lu, L., Malecka-Panas, E., Mambrini, A., Mohelniková-Duchonová, B., Neoptolemos, J.P., Oberg, A.L., Orlow, I., Pasquali, C., Pezzilli, R., Rizzato, C., Saldia, A., Scarpa, A., Stolzenberg-Solomon, R.Z., Strobel, O., Tavano, F., Vashist, Y.K., Vodička, P., Wolpin, B.M., Yu, H., Petersen, G.M., Risch, H.A., Klein, A.P.: (2015) Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer. Nat Genet. 47(8):911-916.

Dowling, P., Hughes, D. J., Larkin, A. M., Meiller, J., Henry, M., Meleady, P., Lynch, V., Pardini, B., Naccarati, A., Levy, M., Vodička, P., Neary, P., Clynes, M.: (2015) Elevated levels of 14-3-3 proteins, serotonin, gamma enolase and pyruvate kinase identified in clinical samples from patients diagnosed with colorectal cancer. Clin. Chim. Acta. 441: 133-141.

Hemminki, K., Frank, C., Försti, A., Musak, L., Kazimirova, A., Barancokova, M., Horska, A., Vymetalková, V., Šmerhovský, Z.,Naccarati, A., Souček, P., Vodičková, L., Buchancová, J., Smolková, B., Dušinská, M., Vodička, P.: (2015) Metabolic gene variants associated with chromosomal aberrations in healthy humans. Gene Chromosomes Cancer. 54(4): 260-266.

Hemminki, K., Rachakonda, S., Musak, L., Vymetálková, V., Halasová, E., Försti, A., Vodičková, L., Buchancová, J., Vodička, P., Kumar, R.: (2015) Telomere length in circulating lymphocytes: Association with chromosomal aberrations. Gene Chromosomes Cancer. 54(3): 194-196.

Pardini, B., Rosa, F., Naccarati, A., Vymetálková, V., Ye, Y., Wu, X., di Gaetano, C., Buchler, T., Novotný, J., Matullo, G., Vodička, P.: (2015) Polymorphisms in microRNA genes as predictors of clinical outcomes in colorectal cancer patients. Carcinogenesis. 31(6): 82-86.

Slyšková, J., Cordero, F., Pardini, B., Korenková, V., Vymetalková, V., Bielik, L., Vodičková, L., Pitule, P., Liska, V., Matejka, V. M., Levy, M., Buchler, T., Kubista, M., Naccarati, A., Vodička, P.: (2015) Post-treatment recovery of suboptimal DNA repair capacity and gene expression levels in colorectal cancer patients. Mol. Carcinog., 54 (9): 769-778.

Vodenková, S., Polivková, Z., Musak, L., Šmerhovský, Z., Zoubková, H., Sytarová, S., Kavcová, E., Halasová, E., Vodičková, L., Jirásková, K., Svoboda, M., Ambrus, M., Hemminki, K., Vodička, P.: (2015) Structural chromosomal aberrations as potential risk markers in incident cancer patients. Mutagenesis.30(4):557-563.

Vodička, P., Caja, F., Vymetálková, V., Procházka, P., Vodičková, L., Schwarzová, L., Slyšková, J., Kumar, R., Schneiderová, M.: (2015) Ile68Met germline variant in exon 2 of the mutL homolog 1 gene in a colorectal cancer patient. Oncol. Lett. 9(1): 183-186.

Vodička, P., Musak, L., Frank, C., Kazimirova, A., Vymetálková, V., Barancoková, M., Smolková, B., Dzupinková, Z., Jirasková, K., Vodenková, S., Kroupa, M., Osina, O., Naccarati, A., Palitti, F., Försti, A., Dusinská, M., Vodičková, L., Hemminki, K.: (2015) Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects. Carcinogenesis.36(11): 1299-1306.

Vymetálková, V., Souček, P., Kunicka, T., Jirásková, K., Brynychova, V., Pardini, B., Novosadova, V., Polivkova, Z., Kubackova, K., Kozevnikovova, R., Ambrus, M., Vodičková, L., Naccarati, A., Vodička, P.: (2015) Genotype and Haplotype Analyses of TP53 Gene in Breast Cancer Patients: Association with Risk and Clinical Outcomes. PLoS One. 10(7): e0134463.

 

2014

Farkas, S. A., Vymetálková, V., Vodičková, L., Vodička, P., Nilsson, T. K.: (2014) DNA methylation changes in genes frequently mutated in sporadic colorectal cancer and in the DNA repair and Wnt/β-catenin signaling pathway genes. Epigenomics 6(2): 179-191.

Huhn, S., Bevier, M., Pardini, B., Naccarati, A., Vodičková, L., Novotny, J., Vodička, P., Hemminki, K., Försti, A.: (2014) Colorectal cancer risk and patients' survival: influence of polymorphisms in genes somatically mutated in colorectal tumors. Cancer Causes Control. 25(6): 759-769.

Kunická, T., Václavíková, R., Hlaváč, V., Vrána, D., Pecha, V., Rauš, K., Trnková, M., Kubáčková, K., Ambruš, M., Vodičková, L., Vodička, P., Souček, P.: (2014) Non-Coding Polymorphisms in Nucleotide Binding Domain 1 in ABCC1 Gene Associate with Transcript Level and Survival of Patients with Breast Cancer. PLoS One 9(7): e101740.

Lu, S., Pardini, B., Cheng, B., Naccarati, A., Huhn, S., Vymetálková, V., Vodičková, L., Buchler, T., Hemminki, K., Vodička, P., Försti, A.: (2014) Single Nucleotide Polymorphisms within Interferon Signaling Pathway Genes Are Associated with Colorectal Cancer Susceptibility and Survival. PLoS One 9(10): e111061.

Makovický, P., Tumova, E., Volek, Z., Makovický, P., Vodičková, L., Slyšková, J., Svoboda, M., Rejhová, A., Vodička, P., Samasca, G., Králová, A., Nagy, M., Mydlarova-Blascaková, M., Poracova, J.: (2014) Histopathological aspects of liver under variable food restriction: Has the intense one-week food restriction a protective effect on non-alcoholic-fatty-liver-disease (NAFLD) development?Pathol. Res. Pract. 210(12): 855-862.

Makovický, P., Tůmová, E., Volek, Z., Makovický, P., Vodička, P.: (2014) Histological aspects of the small intestine under variable feed restriction: The effects of short and intense restriction on a growing rabbit model. Exp. Ther. Med. 8(5): 1623-1627.

Pardini, B., Verderio, P., Pizzamiglio, S., Nici, C., Maiorana, M. V., Naccarati, A., Vodičková, L., Vymetálková, V., Veneroni, S., Daidone, M. G., Ravagnani, F., Bianchi, T., Bujenda, L., Carracedo, A., Castells, A., Ruiz-Ponte, C., Morreau, H., Howarth, K., Jones, A., Castellvı´-Bel, S., Li L., Tomlinson, I., Van Wezel, T., Vodička, P., Radice, P., Peterlongo, P., the EPICOLON Consortium: (2014) Association between CASP8 –652 6N Del Polymorphism (rs3834129) and Colorectal Cancer Risk: Results from a Multi-Centric Study. PLoS ONE 9(3): e91310.

Pardini, B., Bermejo, J. L., Naccarati, A., Di Gaetano, C., Rosa, F., Legrand, C., Novotny, J., Vodička, P., Kumar, R.: (2014) Inherited variability in a master regulator polymorphism (rs4846126) associates with survival in 5-FU treated colorectal cancer patients.Mutat. Res.-Fundam. Mol. Mech. Mutagen. 766-767: 7-13.

Svoboda, M., Slyšková, J., Schneiderova, M., Makovicky, P., Bielik, L., Levy, M., Lipska, L., Hemmelova, B., Kala, Z., Protivankova, M., Vycital, O., Liska, V., Schwarzova, L., Vodičková, L, Vodička P.: (2014) HOTAIR long non-coding RNA is a negative prognostic factor not only in primary tumors, but also in the blood of colorectal cancer patients. Carcinogenesis. 35(7): 1510-1515.

Slyšková, J., Lorenzo, Y., Karlsen, A., Carlsen, M. H., Novosadová, V., Blomhoff, R., Vodička, P., Collins, A. R.: (2014) Both genetic and dietary factors underlie individual differences in DNA damage levels and DNA repair capacity. DNA Repair (Amst). 16 :66-73.

Slyšková, J., Langie, S, A. , Collins, A. R., Vodička, P.: (2014) Functional evaluation of DNA repair in human biopsies and their relation to other cellular biomarkers. Front Genet. 5: 116.

Švec, J., Schwarzová, L., Janošíková, B., Štekrová, J., Mandys, V., Kment, M., Vodička, P.: (2014) Synchronous gastric and sebaceous cancers, a rare manifestation of MLH1-related Muir-Torre syndrome. Int. J. Clin. Exp. Pathol. 7(8): 5196-5202.

Vymetálková, V., Pardini, B., Rosa, F., Di Gaetano, C., Novotny, J., Levy, M., Buchler, T., Slyšková, J., Vodičková, L., Naccarati, A., Vodička, P.: (2014) Variations in mismatch repair genes and colorectal cancer risk and clinical outcome. Mutagenesis. 29(4): 259-265.

Vymetálková, V., Slyšková, J., Korenková, V., Bielik, L., Langerová, L., Procházka, P., Rejhová, A., Schwarzová, L., Pardini, B.,Naccarati, A., Vodička, P.: (2014) Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients BMC Med. Genet. 15(1) :17.

Wolpin, B. M., Rizzato, C., Kraft, P., Kooperberg, C., Petersen, G. M., Wang, Z., Arslan, A. A., Beane-Freeman, L., Bracci, P.M., Buring, J., Canzian, F., Duell, E. J., Gallinger, S., Giles, G. G., Goodman, G. E., Goodman, P. J., Jacobs, E. J., Kamineni, A., Klein, A. P., Kolonel, L. N., Kulke, M. H., Li, D., Malats, N., Olson, S. H., Risch, H. A., Sesso, H. D., Visvanathan, K., White, E., Zheng, W., Abnet, C. C., Albanes, D., Andreotti, G., Austin, M. A., Barfield, R., Basso, D., Berndt, S. I., Boutron-Ruault, M. C., Brotzman, M., Büchler, M. W., Bueno-de-Mesquita, H. B., Bugert, P., Burdette, L., Campa, D., Caporaso, N. E., Capurso, G., Chung, C., Cotterchio, M., Costello, E., Elena, J., Funel, N., Gaziano, J. M., Giese, N. A., Giovannucci, E. L., Goggins, M., Gorman, M. J., Gross, M., Haiman, C. A., Hassan, M., Helzlsouer, K. J., Henderson, B. E., Holly, E. A., Hu, N., Hunter, D. J., Innocenti, F., Jenab, M., Kaaks, R., Key, T. J., Khaw, K. T., Klein, E. A., Kogevinas, M., Krogh, V., Kupcinskas, J., Kurtz, R. C., LaCroix, A., Landi, M. T., Landi, S., Le Marchand, L., Mambrini, A., Mannisto, S., Milne, R. L., Nakamura, Y., Oberg, A. L., Owzar, K., Patel, A. V., Peeters, P. H., Peters, U., Pezzilli, R., Piepoli, A., Porta, M., Real, F. X., Riboli, E., Rothman, N., Scarpa, A., Shu, X. O., Silverman, D. T., Soucek, P., Sund, M., Talar-Wojnarowska, R., Taylor, P. R., Theodoropoulos, G. E., Thornquist, M., Tjønneland, A., Tobias, G. S., Trichopoulos, D., Vodička, P., Wactawski-Wende, J., Wentzensen, N., Wu, C., Yu, H., Yu, K., Zeleniuch-Jacquotte, A., Hoover, R., Hartge, P., Fuchs, C., Chanock, S. J., Stolzenberg-Solomon, R. S., Amundadottir, L. T.: (2014) Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nature Genet. 46(9): 994-1000.

 

2013

Azqueta, A., Langie, S. A., Slyšková, J., Collins, A. R.: (2013) Measurement of DNA base and nucleotide excision repair activities in mammalian cells and tissues using the comet assay - A methodological overview. DNA Repair (Amst) 12: 1007-1010.

Campa, D., Rizzato, C., Capurso, G., Giese, N., Funel, N., Greenhalf, W., Souček, P., Gazouli, M., Pezzilli, R, Pasquali, C., Talar-Wojnarowska, R., Cantore, M., Andriulli, A., Scarpa, A., Jamroziak, K., Delle Fave, G., Costello, E., Khaw, K. T., Heller, A., Key, T. J., Theodoropoulos, G., Malecka-Panas, E., Mambrini, A., Bambi, F., Land, S., Pedrazzoli, S., Bassi, C., Pacetti, P., Piepoli, A., Tavano, F., di Sebastiano, P., Vodičková, L., Basso, D., Plebani, M., Fogar, P., Büchler, M. W., Bugert, P., Vodička, P., Boggi, U., Neoptolemos, J. P., Werner, J., Canzian, F.: (2013) Genetic susceptibility to pancreatic cancer and its functional characterisation: The PANcreatic Disease ReseArch (PANDoRA) consortium. Dig. Liver Dis. 45(2): 95-99.

Campa, D., Rizzato, C., Bauer, A. S., Werner, J., Capurso, G., Costello, E., Talar-Wojnarowska, R., Jamroziak, K., Pezzilli, R., Gazouli, M., Khaw, K. T., Key, T. J., Bambi, F., Mohelnikova-Duchonova, B., Heller, A., Landi, S., Vodičková, L., Theodoropoulos, G., Bugert, P.,Vodička, P., Hoheisel, J., Delle Fave, G., Neoptolemos, J., Souček, P., Buchler, M. W., Giese, N. A., Canzian F.: (2013) Lack of replication of seven pancreatic cancer susceptibility lociidentified in two Asian populations. Cancer Epidemiol. Biomarkers Prev.22(2): 320-323.

Lu, S., Bevier, M., Huhn, S., Sainz, J., Lascorz, J., Pardini, B., Naccarati, A., Vodičková, L., Novotný, J., Hemminki, K., Vodička, P., Försti A.: (2013) Genetic variants in C-type lectin genes are associated with colorectal cancer susceptibility and clinical outcome.Int. J. Cancer. 133(10): 2325-2333.

Makovicky, P., Rimarova, K., Boor, A., Makovicky, P., Vodička, P., Samasca, G., Kruzliak, P.: (2013) Correlation between antibodies and histology in celiac disease: Incidence of celiac disease is higher than expected in the pediatric population. Mol. Med. Rep.8(4): 1079-1083.

Mušák, L., Šmerhovský, Z., Halasová, E., Osina, O., Letková, L., Vodičková, L., Poláková, V., Buchancová, J., Hemminki, K.,Vodička, P.: (2013) Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde. Scand. J. Work Environ. Health. 39(6): 618-630.

Pardini, B., Rosa, F., Barone, E., Di Gaetano, C., Slyšková, J., Novotný, J., Levy, M., Garritano, S., Vodičková, L., Buchler, T., Gemignani, F., Landi, S., Vodička, P., Naccarati, A.: (2013) Variation within 3' UTRs of base excision repair genes and response to therapy in colorectal cancer patients: a potential modulation of microRNAs binding. Clin. Cancer Res. 19(21): 6044-6056.

Picelli, S., Bermejo, J. L., Change-Claude, J., Hoffmeister, M., Fernández-Rozadilla, C., Carracedo, A., Castells, A., Castellví-Bel, S.,Naccarati, A., Pardini, B., Vodičková, L., Hüller, H., Talseth-Palmer, B. A., Stibbard, G., Peterlongo, P., Nici, C., Veneroni, S., Li, L., Casey, G., Tenesa, A., Farrington, S. M., Tomlinson, I., Moreno, V., van Wezel, T., Wijnen, J., Dunlop, M., Radice, P., Scott, R. J.,Vodička, P., Ruiz-Ponte, C., Brenner, H., Buch, S., Völzke, H., Hampe, J., Schafmayer, C., Lindblom, A.: Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility; PLoS One 8(9): e72091.

Poláková-Vymetálková, V., Vannucci, L., Korenková, V., Procházka, P., Slyšková, J., Vodičková, L., Rusňáková, V., Bielik, L., Burocziová, M., Rossmann., P., Vodička, P.: (2013) Evaluation of tumor suppressor gene expressions and aberrant methylation in the colon of cancer-induced rats: a pilot study. Mol. Biol. Rep. 40(10): 5921-5929.

Procházka, P., Hrabeta, J., Vicha, A., Cipro, S., Stejskalová, E., Musil, Z., Vodička, P., Eckschlager, T.: (2013) Changes in MYCN expression in human neuroblastoma cell lines following cisplatin treatment may not be related to MYCN copy numbers. Oncol. Rep. 29(6):2415-2421.

Rizzato, C., Campa, D., Pezzilli, R., Souček, P., Greenhalf, W., Capurso, G., Talar-Wojnarowska, R., Heller, A., Jamroziak, K., Khaw, K. T., Key, T. J., Bambi, F., Landi, S., Mohelniková-Duchoňová, B., Vodičková, L., Büchler, M. W., Bugert. P., Vodička, P., Neoptolemos, J. P., Werner, J., Hoheisel, J. D., Bauer, A. S., Giese, N., Canzian, F.: (2013) ABO blood groups and pancreatic cancer risk and survival: Results from the PANcreatic Disease ReseArch (PANDoRA) consortium. Oncol. Rep. 29(4): 1637-1644.

Czech collaborators:
1. Thomayer hospital Prague
2. IKEM, Prague
3. General teaching hospital, Prague
4. Teaching hospital Pilsen, Pilsen
5. Teaching hospital Kralovské Vinohrady, Prague
6. Masaryk University, Brno
7. First Medical Faculty, Charles University, Prague
8. Third Medical Faculty Charles University, Prague
9. Biomedical Centre, Faculty of Medicine, Pilsen, Charles University Prague
10. National Institute of Public Health, Prague
11. Institue of Biotechnology, CAS v.v.i. Vestec
12. Institute of Molecular Genetics ASCR, Prague
13. Institute of Microbiology ASCR, Prague


International collaborators:
1. DKFZ (German Cancer Research Center) Heidelberg, Germany (prof. Hemminki, prof. Kumar, Dr. Canzian, Dr. Főrsti)
2. University of Pisa, Italy (prof. Landi, prof. Barale, dr. Campa)
3. Human Genetic Foundation, Torino, Italy (Dr. Naccarati, Dr. Pardini)
4. Leiden University Medical Center, Leiden, Netherlands (prof. Van Wezel)
5. IDIBAPS / CIBERehd / Hospital Clínic, Barcelona, Spain (Dr. Castellvi-Bel)
6. Umeå University, Sweden (Prof. Torbjőrn Nilsson)
7. Vienna Medical University, Austria (prof. Knasműller, Dr.Gsur)
8. RCSI Royal College of Surgeons in Ireland, Ireland (dr. Hughes)