11 results on '"Cibula, David"'
Search Results
2. A comprehensive immunohistochemical analysis of IMP2 and IMP3 in 542 cases of ovarian tumors
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Němejcová, Kristýna, Bártů, Michaela Kendall, Michálková, Romana, Drozenová, Jana, Fabian, Pavel, Fadare, Oluwole, Hausnerová, Jitka, Laco, Jan, Matěj, Radoslav, Méhes, Gábor, Singh, Naveena, Stolnicu, Simona, Škapa, Petr, Švajdler, Marián, Stružinská, Ivana, Cibula, David, Kocian, Roman, Lax, Sigurd F., McCluggage, W. Glenn, and Dundr, Pavel
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- 2023
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3. Author Correction: Susceptibility to hormone-mediated cancer is reflected by different tick rates of the epithelial and general epigenetic clock
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Barrett, J. James E., Herzog, Chiara, Kim, Yoo-Na, Bartlett, Thomas E., Jones, Allison, Evans, Iona, Cibula, David, Zikan, Michal, Bjørge, Line, Harbeck, Nadia, Colombo, Nicoletta, Howell, Sacha J., Rådestad, Angelique Flöter, Gemzell-Danielsson, Kristina, and Widschwendter, Martin
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- 2022
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4. DNA methylation-based detection and prediction of cervical intraepithelial neoplasia grade 3 and invasive cervical cancer with the WID™-qCIN test
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Herzog, Chiara, Sundström, Karin, Jones, Allison, Evans, Iona, Barrett, James E., Wang, Jiangrong, Redl, Elisa, Schreiberhuber, Lena, Costas, Laura, Paytubi, Sonia, Dostalek, Lukas, Zikan, Michal, Cibula, David, Sroczynski, Gaby, Siebert, Uwe, Dillner, Joakim, and Widschwendter, Martin
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- 2022
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5. Susceptibility to hormone-mediated cancer is reflected by different tick rates of the epithelial and general epigenetic clock
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Barrett, James E., Herzog, Chiara, Kim, Yoo-Na, Bartlett, Thomas E., Jones, Allison, Evans, Iona, Cibula, David, Zikan, Michal, Bjørge, Line, Harbeck, Nadia, Colombo, Nicoletta, Howell, Sacha J., Rådestad, Angelique Flöter, Gemzell-Danielsson, Kristina, and Widschwendter, Martin
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- 2022
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6. DNA methylation signatures to predict the cervicovaginal microbiome status
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Nené, Nuno R., Barrett, James, Jones, Allison, Evans, Iona, Reisel, Daniel, Timms, John F., Paprotka, Tobias, Leimbach, Andreas, Franchi, Dorella, Colombo, Nicoletta, Bjørge, Line, Zikan, Michal, Cibula, David, and Widschwendter, Martin
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- 2020
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7. Methylation patterns in serum DNA for early identification of disseminated breast cancer
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Widschwendter, Martin, Evans, Iona, Jones, Allison, Ghazali, Shohreh, Reisel, Daniel, Ryan, Andy, Gentry-Maharaj, Aleksandra, Zikan, Michal, Cibula, David, Eichner, Johannes, Alunni-Fabbroni, Marianna, Koch, Julian, Janni, Wolfgang J., Paprotka, Tobias, Wittenberger, Timo, Menon, Usha, Wahl, Benjamin, Rack, Brigitte, and Lempiäinen, Harri
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Adult ,DNA methylation ,lcsh:QH426-470 ,Research ,lcsh:R ,lcsh:Medicine ,Breast Neoplasms ,Middle Aged ,Early diagnosis ,Neoplastic Cells, Circulating ,lcsh:Genetics ,Cell-free DNA ,Serum DNA ,Breast cancer ,Personalized treatment ,Biomarkers, Tumor ,Humans ,Female ,Cell-Free Nucleic Acids ,Aged - Abstract
Background Monitoring treatment and early detection of fatal breast cancer (BC) remains a major unmet need. Aberrant circulating DNA methylation (DNAme) patterns are likely to provide a highly specific cancer signal. We hypothesized that cell-free DNAme markers could indicate disseminated breast cancer, even in the presence of substantial quantities of background DNA. Methods We used reduced representation bisulfite sequencing (RRBS) of 31 tissues and established serum assays based on ultra-high coverage bisulfite sequencing in two independent prospective serum sets (n = 110). The clinical use of one specific region, EFC#93, was validated in 419 patients (in both pre- and post-adjuvant chemotherapy samples) from SUCCESS (Simultaneous Study of Gemcitabine-Docetaxel Combination adjuvant treatment, as well as Extended Bisphosphonate and Surveillance-Trial) and 925 women (pre-diagnosis) from the UKCTOCS (UK Collaborative Trial of Ovarian Cancer Screening) population cohort, with overall survival and occurrence of incident breast cancer (which will or will not lead to death), respectively, as primary endpoints. Results A total of 18 BC specific DNAme patterns were discovered in tissue, of which the top six were further tested in serum. The best candidate, EFC#93, was validated for clinical use. EFC#93 was an independent poor prognostic marker in pre-chemotherapy samples (hazard ratio [HR] for death = 7.689) and superior to circulating tumor cells (CTCs) (HR for death = 5.681). More than 70% of patients with both CTCs and EFC#93 serum DNAme positivity in their pre-chemotherapy samples relapsed within five years. EFC#93-positive disseminated disease in post-chemotherapy samples seems to respond to anti-hormonal treatment. The presence of EFC#93 serum DNAme identified 42.9% and 25% of women who were diagnosed with a fatal BC within 3–6 and 6–12 months of sample donation, respectively, with a specificity of 88%. The sensitivity with respect to detecting fatal BC was ~ 4-fold higher compared to non-fatal BC. Conclusions Detection of EFC#93 serum DNAme patterns offers a new tool for early diagnosis and management of disseminated breast cancers. Clinical trials are required to assess whether EFC#93-positive women in the absence of radiological detectable breast cancers will benefit from anti-hormonal treatment before the breast lesions become clinically apparent. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0499-9) contains supplementary material, which is available to authorized users.
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- 2017
8. The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer.
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Widschwendter, Martin, Zikan, Michal, Wahl, Benjamin, Lempiäinen, Harri, Paprotka, Tobias, Evans, Iona, Jones, Allison, Ghazali, Shohreh, Reisel, Daniel, Eichner, Johannes, Rujan, Tamas, Zhen Yang, Teschendorff, Andrew E., Ryan, Andy, Cibula, David, Menon, Usha, and Wittenberger, Timo
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DNA methylation ,OVARIAN cancer diagnosis ,OVARIAN cancer treatment ,EARLY detection of cancer ,NUCLEOTIDE sequencing ,ADJUVANT treatment of cancer - Abstract
Background: Despite a myriad of attempts in the last three decades to diagnose ovarian cancer (OC) earlier, this clinical aim still remains a significant challenge. Aberrant methylation patterns of linked CpGs analyzed in DNA fragments shed by cancers into the bloodstream (i.e. cell-free DNA) can provide highly specific signals indicating cancer presence. Methods: We analyzed 699 cancerous and non-cancerous tissues using a methylation array or reduced representation bisulfite sequencing to discover the most specific OC methylation patterns. A three-DNAmethylation- serum-marker panel was developed using targeted ultra-high coverage bisulfite sequencing in 151 women and validated in 250 women with various conditions, particularly in those associated with high CA125 levels (endometriosis and other benign pelvic masses), serial samples from 25 patients undergoing neoadjuvant chemotherapy, and a nested case control study of 172 UKCTOCS control arm participants which included serum samples up to two years before OC diagnosis. Results: The cell-free DNA amount and average fragment size in the serum samples was up to ten times higher than average published values (based on samples that were immediately processed) due to leakage of DNA from white blood cells owing to delayed time to serum separation. Despite this, the marker panel discriminated high grade serous OC patients from healthy women or patients with a benign pelvic mass with specificity/sensitivity of 90.7% (95% confidence interval [CI] = 84.3-94.8%) and 41.4% (95% CI = 24.1-60.9%), respectively. Levels of all three markers plummeted after exposure to chemotherapy and correctly identified 78% and 86% responders and non-responders (Fisher's exact test, p = 0.04), respectively, which was superior to a CA125 cut-off of 35 IU/mL (20% and 75%). 57.9% (95% CI 34.0-78.9%) of women who developed OC within two years of sample collection were identified with a specificity of 88.1% (95% CI = 77.3-94.3%). Sensitivity and specificity improved further when specifically analyzing CA125 negative samples only (63.6% and 87.5%, respectively). Conclusions: Our data suggest that DNA methylation patterns in cell-free DNA have the potential to detect a proportion of OCs up to two years in advance of diagnosis and may potentially guide personalized treatment. The prospective use of novel collection vials, which stabilize blood cells and reduce background DNA contamination in serum/plasma samples, will facilitate clinical implementation of liquid biopsy analyses. [ABSTRACT FROM AUTHOR]
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- 2017
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9. Expression of HNF-1β in cervical carcinomas: an immunohistochemical study of 155 cases.
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Němejcová, Kristýna, Cibula, David, and Dundr, Pavel
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GENE expression , *GENETIC regulation , *OLIGONUCLEOTIDE arrays , *ADENOCARCINOMA , *CANCER cells - Abstract
Background: HNF-1β is a commonly used marker in the differential diagnosis of clear cell carcinoma of the ovary and endometrium. Recent studies have found HNF-1β expression to a lesser extent in other ovarian and endometrial tumors including endometrioid, mucinous and, rarely, serous carcinoma. Regarding cervical carcinoma, HNF-1β expression has been mentioned exceptionally in mesonephric and some other types of adenocarcinoma. However, a systematic analysis of HNF-1β expression in cervical carcinomas has not been performed to date. Methods: We analyzed HNF-1β expression in 155 cervical carcinomas (including 56 adenocarcinomas, 85 squamous cell carcinomas and 14 undifferentiated carcinomas). Expression of HNF-1β was correlated with the expression of other markers including estrogen receptors, progesterone receptors, CEA, p63, p40, p16, and D2-40. Results: Adenocarcinomas showed expression of HNF-1β in 42/56 cases (75%), CEA in 48/56 cases (85.7%), p63 in 4/56 cases (7.2%), p40 in 2/56 cases (3.6%), estrogen receptors in 9/56 cases (16.1%), progesterone receptors in 5/56 cases (8.9%), p16 in 56/56 (100%) cases, and D2-40 in 0/56 cases (0%). Squamous cell carcinomas showed expression of HNF-1β in 2/85 cases (2.35%), CEA in 77/85 cases (90.6%), p63 and p40 in 85/85 cases (100%), estrogen receptors in 9/85 cases (10.6%), progesterone receptors in 1/85 cases (1.2%), p16 in 84/85 cases (98.8%), and D2-40 in 45/84 cases (53.6%). Undifferentiated carcinomas showed expression of HNF-1β in 2/14 cases (14.3%), CEA in 8/14 cases (57.1%), p16 in 14/14 cases (100%), hormone receptors in 0/13 cases (0%), p63 in 7/14 cases (50%), p40 in 5/14 cases (35.7%), and D2-40 in 1/14 cases (7.1%). Conclusions: In cervical carcinoma, expression of HNF-1β is mostly restricted to adenocarcinomas and can be used as an auxiliary adenocarcinoma marker in the differential diagnosis of poorly differentiated cervical carcinomas. HNF-1β as an adenocarcinoma marker and p63/p40 and D2-40 as a squamous cell carcinoma markers are highly specific with variable sensitivity. Optimal results can be achieved using these markers in a panel. [ABSTRACT FROM AUTHOR]
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- 2015
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10. A collagen-fibrin patch (Tachosil®) for the prevention of symptomatic lymphoceles after pelvic lymphadenectomy in women with gynecologic malignancies: a randomized clinical trial.
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Grimm, Christoph, Polterauer, Stephan, Helmy, Samir, Cibula, David, Zikan, Michal, Reinthaller, Alexander, and Tempfer, Clemens
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LYMPHOCELE ,LYMPHADENECTOMY ,COLLAGEN ,CLINICAL trials ,GYNECOLOGIC pathology ,PREVENTION - Abstract
Background: Lymphoceles are a common complication after pelvic lymphadenectomy in women with gynecologic malignancies. Although typically asymptomatic, lymphoceles can superinfect requiring medical or surgical intervention. A single center randomized controlled trial provided first evidence, that a collagen-fibrin patch (Tachosil®) is effective in the prevention of symptomatic lymphoceles after pelvic lymphadenectomy. Methods/Design: We will perform a multicentre, blinded, randomized, controlled trial comprising 140 women with gynecologic malignancies undergoing pelvic lymphadenectomy. Women will be randomly allocated to Tachosil® application or no application. Primary outcome is efficacy, defined as lymphocele CTCAE 4.03 grade =2 within four weeks after surgery. Secondary outcomes are asymptomatic lymphocele verified by ultrasound, medical or surgical intervention. Assuming a two-sided 5% significance level, a power of 80%, and a drop out rate of 10%, a sample size of 68 patients per group was calculated to detect a 66% absolute decrease in symptomatic lymphoceles. Discussion: We aim to provide further evidence for the efficacy of a collagen-fibrin patch in the prevention of symptomatic lymphoceles in women with gynecological malignancies undergoing pelvic lymphadenectomy. [ABSTRACT FROM AUTHOR]
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- 2014
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11. A BRCA1-mutation associated DNA methylation signature in blood cells predicts sporadic breast cancer incidence and survival.
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Anjum, Shahzia, Fourkala, Evangelia-Ourania, Zikan, Michal, Wong, Andrew, Gentry-Maharaj, Aleksandra, Jones, Allison, Hardy, Rebecca, Cibula, David, Kuh, Diana, Jacobs, Ian J., Teschendorff, Andrew E., Menon, Usha, and Widschwendter, Martin
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BREAST cancer ,CANCER risk factors ,EARLY detection of cancer ,GENETIC mutation ,DNA methylation ,COHORT analysis ,EPITHELIAL cells ,STEM cells - Abstract
Background BRCA1 mutation carriers have an 85% risk of developing breast cancer but the risk of developing non-hereditary breast cancer is difficult to assess. Our objective is to test whether a DNA methylation (DNAme) signature derived from BRCA1 mutation carriers is able to predict non-hereditary breast cancer. Methods In a case/control setting (72 BRCA1 mutation carriers and 72 BRCA1/2 wild type controls) blood cell DNA samples were profiled on the Illumina 27 k methylation array. Using the Elastic Net classification algorithm, a BRCA1-mutation DNAme signature was derived and tested in two cohorts: (i) The NSHD (19 breast cancers developed within 12 years after sample donation and 77 controls) and (ii) the UKCTOCS trial (119 estrogen receptor positive breast cancers developed within 5 years after sample donation and 122 controls). Results We found that our blood based BRCA1-mutation DNAme signature applied to blood cell DNA from women in the NSHD resulted in a Receiver Operating Characteristics (ROC) Area Under the Curve (AUC) of 0.65 (95% CI 0.51-0.78, P = 0.02) which did not validate in buccal cells from the same individuals. Applying the signature in blood DNA from UKCTOCS volunteers resulted in AUC of 0.57 (95% CI 0.50-0.64; P = 0.03) and is independent of family history or any other known risk factors. Importantly the BRCA1- mutation DNAme signature was able to predict breast cancer mortality (AUC = 0.67; 95% CI 0.51-0.83) P = 0.02). We also found that the 1074 CpGs which are hypermethylated in BRCA1 mutation carriers are massively enriched for stem cell polycomb group target genes (P < 10
-20 ). Conclusions A DNAme signature derived from BRCA1 carriers is able to predict breast cancer risk and death years in advance of diagnosis. Future studies may need to focus on DNAme profiles in epithelial cells in order to reach the AUC thresholds required of preventative measures or early detection strategies. [ABSTRACT FROM AUTHOR]- Published
- 2014
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