Medical Statistics

KPNA2 Is Overexpressed in Human and Mouse Endometrial Cancers and Promotes Cellular Proliferation.
Kristian Ikenberg, Nadejda Valtcheva, Simone Brandt, Qing Zhong, Christine E. Wong, Aurelia Noske, Markus Rechsteiner, Jan H. Rueschoff, Rosemarie Caduff, Athanassios Dellas, Ellen Obermann, Daniel Fink, Thomas J. Fuchs, Wilhelm Krek, Holger Moch, Ian J. Frew and Peter J. Wild.
The Journal of Pathology, vol. 234, 2, p. 239–252, 2014
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@article{ikenberg_kpna2_2014,
    title = {{KPNA}2 {Is} {Overexpressed} in {Human} and {Mouse} {Endometrial} {Cancers} and {Promotes} {Cellular} {Proliferation}},
    volume = {234},
    issn = {1096-9896},
    url = {http://dx.doi.org/10.1002/path.4390},
    doi = {10.1002/path.4390},
    number = {2},
    journal = {The Journal of Pathology},
    author = {Ikenberg, Kristian and Valtcheva, Nadejda and Brandt, Simone and Zhong, Qing and Wong, Christine E. and Noske, Aurelia and Rechsteiner, Markus and Rueschoff, Jan H. and Caduff, Rosemarie and Dellas, Athanassios and Obermann, Ellen and Fink, Daniel and Fuchs, Thomas J. and Krek, Wilhelm and Moch, Holger and Frew, Ian J. and Wild, Peter J.},
    year = {2014},
    keywords = {EMT, KPNA2, Snail, biomarker, endometrial cancer, importin},
    pages = {239--252}
}
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TY - JOUR
TI - KPNA2 Is Overexpressed in Human and Mouse Endometrial Cancers and Promotes Cellular Proliferation
AU - Ikenberg, Kristian
AU - Valtcheva, Nadejda
AU - Brandt, Simone
AU - Zhong, Qing
AU - Wong, Christine E.
AU - Noske, Aurelia
AU - Rechsteiner, Markus
AU - Rueschoff, Jan H.
AU - Caduff, Rosemarie
AU - Dellas, Athanassios
AU - Obermann, Ellen
AU - Fink, Daniel
AU - Fuchs, Thomas J.
AU - Krek, Wilhelm
AU - Moch, Holger
AU - Frew, Ian J.
AU - Wild, Peter J.
T2 - The Journal of Pathology
DA - 2014///
PY - 2014
DO - 10.1002/path.4390
VL - 234
IS - 2
SP - 239
EP - 252
SN - 1096-9896
UR - http://dx.doi.org/10.1002/path.4390
KW - EMT
KW - KPNA2
KW - Snail
KW - biomarker
KW - endometrial cancer
KW - importin
ER -
A Seven-Marker Signature and Clinical Outcome in Malignant Melanoma: A Large-Scale Tissue-Microarray Study with Two Independent Patient Cohorts.
Stefanie Meyer, Thomas J. Fuchs, Anja K. Bosserhoff, Ferdinand Hofstädter, Armin Pauer, Volker Roth, Joachim M. Buhmann, Ingrid Moll, Nikos Anagnostou, Johanna M. Brandner, Kristian Ikenberg, Holger Moch, Michael Landthaler, Thomas Vogt and Peter J. Wild.
PLoS ONE, vol. 7, 6, p. e38222, 2012
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@article{meyer_seven-marker_2012,
    title = {A {Seven}-{Marker} {Signature} and {Clinical} {Outcome} in {Malignant} {Melanoma}: {A} {Large}-{Scale} {Tissue}-{Microarray} {Study} with {Two} {Independent} {Patient} {Cohorts}},
    volume = {7},
    shorttitle = {A {Seven}-{Marker} {Signature} and {Clinical} {Outcome} in {Malignant} {Melanoma}},
    url = {http://dx.doi.org/10.1371/journal.pone.0038222},
    doi = {10.1371/journal.pone.0038222},
    abstract = {BackgroundCurrent staging methods such as tumor thickness, ulceration and invasion of the sentinel node are known to be prognostic parameters in patients with malignant melanoma (MM). However, predictive molecular marker profiles for risk stratification and therapy optimization are not yet available for routine clinical assessment.Methods and FindingsUsing tissue microarrays, we retrospectively analyzed samples from 364 patients with primary MM. We investigated a panel of 70 immunohistochemical (IHC) antibodies for cell cycle, apoptosis, DNA mismatch repair, differentiation, proliferation, cell adhesion, signaling and metabolism. A marker selection procedure based on univariate Cox regression and multiple testing correction was employed to correlate the IHC expression data with the clinical follow-up (overall and recurrence-free survival). The model was thoroughly evaluated with two different cross validation experiments, a permutation test and a multivariate Cox regression analysis. In addition, the predictive power of the identified marker signature was validated on a second independent external test cohort (n = 225). A signature of seven biomarkers (Bax, Bcl-X, PTEN, COX-2, loss of β-Catenin, loss of MTAP, and presence of CD20 positive B-lymphocytes) was found to be an independent negative predictor for overall and recurrence-free survival in patients with MM. The seven-marker signature could also predict a high risk of disease recurrence in patients with localized primary MM stage pT1-2 (tumor thickness ≤2.00 mm). In particular, three of these markers (MTAP, COX-2, Bcl-X) were shown to offer direct therapeutic implications.ConclusionsThe seven-marker signature might serve as a prognostic tool enabling physicians to selectively triage, at the time of diagnosis, the subset of high recurrence risk stage I–II patients for adjuvant therapy. Selective treatment of those patients that are more likely to develop distant metastatic disease could potentially lower the burden of untreatable metastatic melanoma and revolutionize the therapeutic management of MM.},
    number = {6},
    urldate = {2016-01-03TZ},
    journal = {PLoS ONE},
    author = {Meyer, Stefanie and Fuchs, Thomas J. and Bosserhoff, Anja K. and Hofst\"adter, Ferdinand and Pauer, Armin and Roth, Volker and Buhmann, Joachim M. and Moll, Ingrid and Anagnostou, Nikos and Brandner, Johanna M. and Ikenberg, Kristian and Moch, Holger and Landthaler, Michael and Vogt, Thomas and Wild, Peter J.},
    year = {2012},
    pages = {e38222}
}
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TY - JOUR
TI - A Seven-Marker Signature and Clinical Outcome in Malignant Melanoma: A Large-Scale Tissue-Microarray Study with Two Independent Patient Cohorts
AU - Meyer, Stefanie
AU - Fuchs, Thomas J.
AU - Bosserhoff, Anja K.
AU - Hofstädter, Ferdinand
AU - Pauer, Armin
AU - Roth, Volker
AU - Buhmann, Joachim M.
AU - Moll, Ingrid
AU - Anagnostou, Nikos
AU - Brandner, Johanna M.
AU - Ikenberg, Kristian
AU - Moch, Holger
AU - Landthaler, Michael
AU - Vogt, Thomas
AU - Wild, Peter J.
T2 - PLoS ONE
AB - BackgroundCurrent staging methods such as tumor thickness, ulceration and invasion of the sentinel node are known to be prognostic parameters in patients with malignant melanoma (MM). However, predictive molecular marker profiles for risk stratification and therapy optimization are not yet available for routine clinical assessment.Methods and FindingsUsing tissue microarrays, we retrospectively analyzed samples from 364 patients with primary MM. We investigated a panel of 70 immunohistochemical (IHC) antibodies for cell cycle, apoptosis, DNA mismatch repair, differentiation, proliferation, cell adhesion, signaling and metabolism. A marker selection procedure based on univariate Cox regression and multiple testing correction was employed to correlate the IHC expression data with the clinical follow-up (overall and recurrence-free survival). The model was thoroughly evaluated with two different cross validation experiments, a permutation test and a multivariate Cox regression analysis. In addition, the predictive power of the identified marker signature was validated on a second independent external test cohort (n = 225). A signature of seven biomarkers (Bax, Bcl-X, PTEN, COX-2, loss of β-Catenin, loss of MTAP, and presence of CD20 positive B-lymphocytes) was found to be an independent negative predictor for overall and recurrence-free survival in patients with MM. The seven-marker signature could also predict a high risk of disease recurrence in patients with localized primary MM stage pT1-2 (tumor thickness ≤2.00 mm). In particular, three of these markers (MTAP, COX-2, Bcl-X) were shown to offer direct therapeutic implications.ConclusionsThe seven-marker signature might serve as a prognostic tool enabling physicians to selectively triage, at the time of diagnosis, the subset of high recurrence risk stage I–II patients for adjuvant therapy. Selective treatment of those patients that are more likely to develop distant metastatic disease could potentially lower the burden of untreatable metastatic melanoma and revolutionize the therapeutic management of MM.
DA - 2012///
PY - 2012
DO - 10.1371/journal.pone.0038222
DP - PLoS Journals
VL - 7
IS - 6
SP - e38222
J2 - PLoS ONE
ST - A Seven-Marker Signature and Clinical Outcome in Malignant Melanoma
UR - http://dx.doi.org/10.1371/journal.pone.0038222
Y2 - 2016/01/03/T15:45:02Z
ER -
BackgroundCurrent staging methods such as tumor thickness, ulceration and invasion of the sentinel node are known to be prognostic parameters in patients with malignant melanoma (MM). However, predictive molecular marker profiles for risk stratification and therapy optimization are not yet available for routine clinical assessment.Methods and FindingsUsing tissue microarrays, we retrospectively analyzed samples from 364 patients with primary MM. We investigated a panel of 70 immunohistochemical (IHC) antibodies for cell cycle, apoptosis, DNA mismatch repair, differentiation, proliferation, cell adhesion, signaling and metabolism. A marker selection procedure based on univariate Cox regression and multiple testing correction was employed to correlate the IHC expression data with the clinical follow-up (overall and recurrence-free survival). The model was thoroughly evaluated with two different cross validation experiments, a permutation test and a multivariate Cox regression analysis. In addition, the predictive power of the identified marker signature was validated on a second independent external test cohort (n = 225). A signature of seven biomarkers (Bax, Bcl-X, PTEN, COX-2, loss of β-Catenin, loss of MTAP, and presence of CD20 positive B-lymphocytes) was found to be an independent negative predictor for overall and recurrence-free survival in patients with MM. The seven-marker signature could also predict a high risk of disease recurrence in patients with localized primary MM stage pT1-2 (tumor thickness ≤2.00 mm). In particular, three of these markers (MTAP, COX-2, Bcl-X) were shown to offer direct therapeutic implications.ConclusionsThe seven-marker signature might serve as a prognostic tool enabling physicians to selectively triage, at the time of diagnosis, the subset of high recurrence risk stage I–II patients for adjuvant therapy. Selective treatment of those patients that are more likely to develop distant metastatic disease could potentially lower the burden of untreatable metastatic melanoma and revolutionize the therapeutic management of MM.
p53 Suppresses Type II Endometrial Carcinomas in Mice and Governs Endometrial Tumour Aggressiveness in Humans.
Peter J. Wild, Kristian Ikenberg, Thomas J. Fuchs, Markus Rechsteiner, Strahil Georgiev, Niklaus Fankhauser, Aurelia Noske, Matthias Roessle, Rosmarie Caduff, Athanassios Dellas, Daniel Fink, Holger Moch, Wilhelm Krek and Ian J. Frew.
EMBO Molecular Medicine, vol. 4, 8, p. 808-824, 2012
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@article{wild_p53_2012,
    title = {p53 {Suppresses} {Type} {II} {Endometrial} {Carcinomas} in {Mice} and {Governs} {Endometrial} {Tumour} {Aggressiveness} in {Humans}},
    volume = {4},
    issn = {17574676},
    shorttitle = {p53 suppresses type {II} endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans},
    url = {http://embomolmed.embopress.org/cgi/doi/10.1002/emmm.201101063},
    doi = {10.1002/emmm.201101063},
    abstract = {Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours.},
    language = {en},
    number = {8},
    urldate = {2016-04-12TZ},
    journal = {EMBO Molecular Medicine},
    author = {Wild, Peter J. and Ikenberg, Kristian and Fuchs, Thomas J. and Rechsteiner, Markus and Georgiev, Strahil and Fankhauser, Niklaus and Noske, Aurelia and Roessle, Matthias and Caduff, Rosmarie and Dellas, Athanassios and Fink, Daniel and Moch, Holger and Krek, Wilhelm and Frew, Ian J.},
    year = {2012},
    pages = {808--824}
}
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TY - JOUR
TI - p53 Suppresses Type II Endometrial Carcinomas in Mice and Governs Endometrial Tumour Aggressiveness in Humans
AU - Wild, Peter J.
AU - Ikenberg, Kristian
AU - Fuchs, Thomas J.
AU - Rechsteiner, Markus
AU - Georgiev, Strahil
AU - Fankhauser, Niklaus
AU - Noske, Aurelia
AU - Roessle, Matthias
AU - Caduff, Rosmarie
AU - Dellas, Athanassios
AU - Fink, Daniel
AU - Moch, Holger
AU - Krek, Wilhelm
AU - Frew, Ian J.
T2 - EMBO Molecular Medicine
AB - Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours.
DA - 2012///
PY - 2012
DO - 10.1002/emmm.201101063
DP - CrossRef
VL - 4
IS - 8
SP - 808
EP - 824
LA - en
SN - 17574676
ST - p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans
UR - http://embomolmed.embopress.org/cgi/doi/10.1002/emmm.201101063
Y2 - 2016/04/12/T13:58:18Z
ER -
Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours.
A High-Throughput Metabolomics Method to Predict High Concentration Cytotoxicity of Drugs from Low Concentration Profiles.
Stephanie Heux, Thomas J. Fuchs, Joachim Buhmann, Nicola Zamboni and Uwe Sauer.
Metabolomics, vol. 8, 3, p. 433-443, 2012
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@article{heux_high-throughput_2012,
    title = {A {High}-{Throughput} {Metabolomics} {Method} to {Predict} {High} {Concentration} {Cytotoxicity} of {Drugs} from {Low} {Concentration} {Profiles}},
    volume = {8},
    issn = {1573-3882},
    url = {http://dx.doi.org/10.1007/s11306-011-0386-0},
    doi = {10.1007/s11306-011-0386-0},
    number = {3},
    journal = {Metabolomics},
    author = {Heux, Stephanie and Fuchs, Thomas J. and Buhmann, Joachim and Zamboni, Nicola and Sauer, Uwe},
    year = {2012},
    keywords = {Biomedical and Life Sciences},
    pages = {433--443}
}
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TY - JOUR
TI - A High-Throughput Metabolomics Method to Predict High Concentration Cytotoxicity of Drugs from Low Concentration Profiles
AU - Heux, Stephanie
AU - Fuchs, Thomas J.
AU - Buhmann, Joachim
AU - Zamboni, Nicola
AU - Sauer, Uwe
T2 - Metabolomics
DA - 2012///
PY - 2012
DO - 10.1007/s11306-011-0386-0
VL - 8
IS - 3
SP - 433
EP - 443
SN - 1573-3882
UR - http://dx.doi.org/10.1007/s11306-011-0386-0
KW - Biomedical and Life Sciences
ER -
Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice.
Johannes Haybaeck, Mathias Heikenwalder, Britta Klevenz, Petra Schwarz, Ilan Margalith, Claire Bridel, Kirsten Mertz, Elizabeta Zirdum, Benjamin Petsch, Thomas J. Fuchs, Lothar Stitz and Adriano Aguzzi.
PLoS Pathog, vol. 7, 1, p. e1001257, 2011
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@article{haybaeck_aerosols_2011,
    title = {Aerosols {Transmit} {Prions} to {Immunocompetent} and {Immunodeficient} {Mice}},
    volume = {7},
    url = {http://dx.doi.org/10.1371/journal.ppat.1001257},
    doi = {10.1371/journal.ppat.1001257},
    abstract = {Author Summary
    Prions, which are the cause of fatal neurodegenerative disorders termed transmissible spongiform encephalopathies (TSEs), can be experimentally or naturally transmitted via prion-contaminated food, blood, milk, saliva, feces and urine. Here we demonstrate that prions can be transmitted through aerosols in mice. This also occurs in the absence of immune cells as demonstrated by experiments with mice lacking B-, T-, follicular dendritic cells (FDCs), lymphotoxin signaling or with complement-deficient mice. Therefore, a functionally intact immune system is not strictly needed for aerogenic prion infection. These results suggest that current biosafety guidelines applied in diagnostic and scientific laboratories ought to include prion aerosols as a potential vector for prion infection.},
    number = {1},
    urldate = {2016-01-03TZ},
    journal = {PLoS Pathog},
    author = {Haybaeck, Johannes and Heikenwalder, Mathias and Klevenz, Britta and Schwarz, Petra and Margalith, Ilan and Bridel, Claire and Mertz, Kirsten and Zirdum, Elizabeta and Petsch, Benjamin and Fuchs, Thomas J. and Stitz, Lothar and Aguzzi, Adriano},
    year = {2011},
    pages = {e1001257}
}
Download Endnote/RIS citation
TY - JOUR
TI - Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice
AU - Haybaeck, Johannes
AU - Heikenwalder, Mathias
AU - Klevenz, Britta
AU - Schwarz, Petra
AU - Margalith, Ilan
AU - Bridel, Claire
AU - Mertz, Kirsten
AU - Zirdum, Elizabeta
AU - Petsch, Benjamin
AU - Fuchs, Thomas J.
AU - Stitz, Lothar
AU - Aguzzi, Adriano
T2 - PLoS Pathog
AB - Author Summary
Prions, which are the cause of fatal neurodegenerative disorders termed transmissible spongiform encephalopathies (TSEs), can be experimentally or naturally transmitted via prion-contaminated food, blood, milk, saliva, feces and urine. Here we demonstrate that prions can be transmitted through aerosols in mice. This also occurs in the absence of immune cells as demonstrated by experiments with mice lacking B-, T-, follicular dendritic cells (FDCs), lymphotoxin signaling or with complement-deficient mice. Therefore, a functionally intact immune system is not strictly needed for aerogenic prion infection. These results suggest that current biosafety guidelines applied in diagnostic and scientific laboratories ought to include prion aerosols as a potential vector for prion infection.
DA - 2011///
PY - 2011
DO - 10.1371/journal.ppat.1001257
DP - PLoS Journals
VL - 7
IS - 1
SP - e1001257
J2 - PLoS Pathog
UR - http://dx.doi.org/10.1371/journal.ppat.1001257
Y2 - 2016/01/03/T16:08:54Z
ER -
Author Summary Prions, which are the cause of fatal neurodegenerative disorders termed transmissible spongiform encephalopathies (TSEs), can be experimentally or naturally transmitted via prion-contaminated food, blood, milk, saliva, feces and urine. Here we demonstrate that prions can be transmitted through aerosols in mice. This also occurs in the absence of immune cells as demonstrated by experiments with mice lacking B-, T-, follicular dendritic cells (FDCs), lymphotoxin signaling or with complement-deficient mice. Therefore, a functionally intact immune system is not strictly needed for aerogenic prion infection. These results suggest that current biosafety guidelines applied in diagnostic and scientific laboratories ought to include prion aerosols as a potential vector for prion infection.
Cancer Genetics-Guided Discovery of Serum Biomarker Signatures for Diagnosis and Prognosis of Prostate Cancer.
Igor Cima, Ralph Schiess, Peter Wild, Martin Kaelin, Peter Schueffler, Vinzenz Lange, Paola Picotti, Reto Ossola, Arnoud Templeton, Olga Schubert, Thomas J. Fuchs, Thomas Leippold, Stephen Wyler, Jens Zehetner, Wolfram Jochum, Joachim Buhmann, Thomas Cerny, Holger Moch, Silke Gillessen, Ruedi Aebersold and Wilhelm Krek.
PNAS: Proceedings of the National Academy of Sciences, vol. 108, 8, p. 3342-3347, 2011
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@article{cima_cancer_2011,
    title = {Cancer {Genetics}-{Guided} {Discovery} of {Serum} {Biomarker} {Signatures} for {Diagnosis} and {Prognosis} of {Prostate} {Cancer}},
    volume = {108},
    url = {http://www.pnas.org/content/108/8/3342.abstract},
    doi = {10.1073/pnas.1013699108},
    abstract = {A key barrier to the realization of personalized medicine for cancer is the identification of biomarkers. Here we describe a two-stage strategy for the discovery of serum biomarker signatures corresponding to specific cancer-causing mutations and its application to prostate cancer (PCa) in the context of the commonly occurring phosphatase and tensin homolog (PTEN) tumor-suppressor gene inactivation. In the first stage of our approach, we identified 775 N-linked glycoproteins from sera and prostate tissue of wild-type and Pten-null mice. Using label-free quantitative proteomics, we showed that Pten inactivation leads to measurable perturbations in the murine prostate and serum glycoproteome. Following bioinformatic prioritization, in a second stage we applied targeted proteomics to detect and quantify 39 human ortholog candidate biomarkers in the sera of PCa patients and control individuals. The resulting proteomic profiles were analyzed by machine learning to build predictive regression models for tissue PTEN status and diagnosis and grading of PCa. Our approach suggests a general path to rational cancer biomarker discovery and initial validation guided by cancer genetics and based on the integration of experimental mouse models, proteomics-based technologies, and computational modeling.},
    number = {8},
    journal = {PNAS: Proceedings of the National Academy of Sciences},
    author = {Cima, Igor and Schiess, Ralph and Wild, Peter and Kaelin, Martin and Schueffler, Peter and Lange, Vinzenz and Picotti, Paola and Ossola, Reto and Templeton, Arnoud and Schubert, Olga and Fuchs, Thomas J. and Leippold, Thomas and Wyler, Stephen and Zehetner, Jens and Jochum, Wolfram and Buhmann, Joachim and Cerny, Thomas and Moch, Holger and Gillessen, Silke and Aebersold, Ruedi and Krek, Wilhelm},
    year = {2011},
    pages = {3342--3347}
}
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TY - JOUR
TI - Cancer Genetics-Guided Discovery of Serum Biomarker Signatures for Diagnosis and Prognosis of Prostate Cancer
AU - Cima, Igor
AU - Schiess, Ralph
AU - Wild, Peter
AU - Kaelin, Martin
AU - Schueffler, Peter
AU - Lange, Vinzenz
AU - Picotti, Paola
AU - Ossola, Reto
AU - Templeton, Arnoud
AU - Schubert, Olga
AU - Fuchs, Thomas J.
AU - Leippold, Thomas
AU - Wyler, Stephen
AU - Zehetner, Jens
AU - Jochum, Wolfram
AU - Buhmann, Joachim
AU - Cerny, Thomas
AU - Moch, Holger
AU - Gillessen, Silke
AU - Aebersold, Ruedi
AU - Krek, Wilhelm
T2 - PNAS: Proceedings of the National Academy of Sciences
AB - A key barrier to the realization of personalized medicine for cancer is the identification of biomarkers. Here we describe a two-stage strategy for the discovery of serum biomarker signatures corresponding to specific cancer-causing mutations and its application to prostate cancer (PCa) in the context of the commonly occurring phosphatase and tensin homolog (PTEN) tumor-suppressor gene inactivation. In the first stage of our approach, we identified 775 N-linked glycoproteins from sera and prostate tissue of wild-type and Pten-null mice. Using label-free quantitative proteomics, we showed that Pten inactivation leads to measurable perturbations in the murine prostate and serum glycoproteome. Following bioinformatic prioritization, in a second stage we applied targeted proteomics to detect and quantify 39 human ortholog candidate biomarkers in the sera of PCa patients and control individuals. The resulting proteomic profiles were analyzed by machine learning to build predictive regression models for tissue PTEN status and diagnosis and grading of PCa. Our approach suggests a general path to rational cancer biomarker discovery and initial validation guided by cancer genetics and based on the integration of experimental mouse models, proteomics-based technologies, and computational modeling.
DA - 2011///
PY - 2011
DO - 10.1073/pnas.1013699108
VL - 108
IS - 8
SP - 3342
EP - 3347
UR - http://www.pnas.org/content/108/8/3342.abstract
ER -
A key barrier to the realization of personalized medicine for cancer is the identification of biomarkers. Here we describe a two-stage strategy for the discovery of serum biomarker signatures corresponding to specific cancer-causing mutations and its application to prostate cancer (PCa) in the context of the commonly occurring phosphatase and tensin homolog (PTEN) tumor-suppressor gene inactivation. In the first stage of our approach, we identified 775 N-linked glycoproteins from sera and prostate tissue of wild-type and Pten-null mice. Using label-free quantitative proteomics, we showed that Pten inactivation leads to measurable perturbations in the murine prostate and serum glycoproteome. Following bioinformatic prioritization, in a second stage we applied targeted proteomics to detect and quantify 39 human ortholog candidate biomarkers in the sera of PCa patients and control individuals. The resulting proteomic profiles were analyzed by machine learning to build predictive regression models for tissue PTEN status and diagnosis and grading of PCa. Our approach suggests a general path to rational cancer biomarker discovery and initial validation guided by cancer genetics and based on the integration of experimental mouse models, proteomics-based technologies, and computational modeling.
TAK1 Suppresses a NEMO-Dependent but NF-kappaB-Independent Pathway to Liver Cancer.
Kira Bettermann, Mihael Vucur, Johannes Haybaeck, Christiane Koppe, Joern Janssen, Felix Heymann, Achim Weber, Ralf Weiskirchen, Christian Liedtke, Nikolaus Gassler, Michael Mueller, Rita de Vos, Monika Julia Wolf, Yannick Boege, Gitta Maria Seleznik, Nicolas Zeller, Daniel Erny, Thomas J. Fuchs, Stefan Zoller, Stefano Cairo, Marie-Annick Buendia, Marco Prinz, Shizuo Akira, Frank Tacke, Mathias Heikenwaelder, Christian Trautwein and Tom Luedde.
Cancer Cell, vol. 17, 5, p. 481–496, 2010
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@article{bettermann_tak1_2010,
    title = {{TAK}1 {Suppresses} a {NEMO}-{Dependent} but {NF}-{kappaB}-{Independent} {Pathway} to {Liver} {Cancer}},
    volume = {17},
    url = {http://www.ncbi.nlm.nih.gov/pubmed/20478530},
    number = {5},
    journal = {Cancer Cell},
    author = {Bettermann, Kira and Vucur, Mihael and Haybaeck, Johannes and Koppe, Christiane and Janssen, Joern and Heymann, Felix and Weber, Achim and Weiskirchen, Ralf and Liedtke, Christian and Gassler, Nikolaus and Mueller, Michael and de Vos, Rita and Wolf, Monika Julia and Boege, Yannick and Seleznik, Gitta Maria and Zeller, Nicolas and Erny, Daniel and Fuchs, Thomas J. and Zoller, Stefan and Cairo, Stefano and Buendia, Marie-Annick and Prinz, Marco and Akira, Shizuo and Tacke, Frank and Heikenwaelder, Mathias and Trautwein, Christian and Luedde, Tom},
    year = {2010},
    pages = {481--496}
}
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TY - JOUR
TI - TAK1 Suppresses a NEMO-Dependent but NF-kappaB-Independent Pathway to Liver Cancer
AU - Bettermann, Kira
AU - Vucur, Mihael
AU - Haybaeck, Johannes
AU - Koppe, Christiane
AU - Janssen, Joern
AU - Heymann, Felix
AU - Weber, Achim
AU - Weiskirchen, Ralf
AU - Liedtke, Christian
AU - Gassler, Nikolaus
AU - Mueller, Michael
AU - de Vos, Rita
AU - Wolf, Monika Julia
AU - Boege, Yannick
AU - Seleznik, Gitta Maria
AU - Zeller, Nicolas
AU - Erny, Daniel
AU - Fuchs, Thomas J.
AU - Zoller, Stefan
AU - Cairo, Stefano
AU - Buendia, Marie-Annick
AU - Prinz, Marco
AU - Akira, Shizuo
AU - Tacke, Frank
AU - Heikenwaelder, Mathias
AU - Trautwein, Christian
AU - Luedde, Tom
T2 - Cancer Cell
DA - 2010///
PY - 2010
VL - 17
IS - 5
SP - 481
EP - 496
UR - http://www.ncbi.nlm.nih.gov/pubmed/20478530
ER -
Nuclear Detection of Y-Box Protein-1 (YB-1) Closely Associates with Progesterone Receptor Negativity and Is a Strong Adverse Survival Factor in Human Breast Cancer.
Edgar Dahl, Abdelaziz En-Nia, Frank Wiesmann, Renate Krings, Sonja Djudjaj, Elisabeth Breuer, Thomas J. Fuchs, Peter Wild, Arndt Hartmann, Sandra Dunn and Peter Mertens.
BMC Cancer, vol. 9, 1, p. 410, 2009
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@article{dahl_nuclear_2009,
    title = {Nuclear {Detection} of {Y}-{Box} {Protein}-1 ({YB}-1) {Closely} {Associates} with {Progesterone} {Receptor} {Negativity} and {Is} a {Strong} {Adverse} {Survival} {Factor} in {Human} {Breast} {Cancer}},
    volume = {9},
    issn = {1471-2407},
    url = {http://www.biomedcentral.com/1471-2407/9/410},
    doi = {10.1186/1471-2407-9-410},
    number = {1},
    journal = {BMC Cancer},
    author = {Dahl, Edgar and En-Nia, Abdelaziz and Wiesmann, Frank and Krings, Renate and Djudjaj, Sonja and Breuer, Elisabeth and Fuchs, Thomas J. and Wild, Peter and Hartmann, Arndt and Dunn, Sandra and Mertens, Peter},
    year = {2009},
    pages = {410}
}
Download Endnote/RIS citation
TY - JOUR
TI - Nuclear Detection of Y-Box Protein-1 (YB-1) Closely Associates with Progesterone Receptor Negativity and Is a Strong Adverse Survival Factor in Human Breast Cancer
AU - Dahl, Edgar
AU - En-Nia, Abdelaziz
AU - Wiesmann, Frank
AU - Krings, Renate
AU - Djudjaj, Sonja
AU - Breuer, Elisabeth
AU - Fuchs, Thomas J.
AU - Wild, Peter
AU - Hartmann, Arndt
AU - Dunn, Sandra
AU - Mertens, Peter
T2 - BMC Cancer
DA - 2009///
PY - 2009
DO - 10.1186/1471-2407-9-410
VL - 9
IS - 1
SP - 410
SN - 1471-2407
UR - http://www.biomedcentral.com/1471-2407/9/410
ER -
Detection of Urothelial Bladder Cancer Cells in Voided Urine Can Be Improved by a Combination of Cytology and Standardized Microsatellite Analysis.
Peter J. Wild, Thomas J. Fuchs, Robert Stoehr, Dieter Zimmermann, Simona Frigerio, Barbara Padberg, Inbal Steiner, Ellen C. Zwarthoff, Maximilian Burger, Stefan Denzinger, Ferdinand Hofstaedter, Glen Kristiansen, Thomas Hermanns, Hans-Helge Seifert, Maurizio Provenzano, Tullio Sulser, Volker Roth, Joachim M. Buhmann, Holger Moch and Arndt Hartmann.
Cancer Epidemiol Biomarkers Prev, vol. 18, 6, p. 1798-1806, 2009
PDF   URL   BibTeX   Endnote / RIS   Abstract
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@article{wild_detection_2009,
    title = {Detection of {Urothelial} {Bladder} {Cancer} {Cells} in {Voided} {Urine} {Can} {Be} {Improved} by a {Combination} of {Cytology} and {Standardized} {Microsatellite} {Analysis}},
    volume = {18},
    url = {http://cebp.aacrjournals.org/cgi/content/abstract/18/6/1798},
    doi = {10.1158/1055-9965.EPI-09-0099},
    abstract = {Purpose: To evaluate molecular and immunohistochemical markers to develop a molecular grading of urothelial bladder cancer and to test these markers in voided urine samples.
    Experimental Design: 255 consecutive biopsies from primary bladder cancer patients were evaluated on a tissue microarray. The clinical parameters gender, age, adjacent carcinoma in situ, and multifocality were collected. UroVysion fluorescence in situ hybridization (FISH) was done. Expression of cytokeratin 20, MIB1, and TP53 was analyzed by immunohistochemistry. Fibroblast growth factor receptor 3 (FGFR3) status was studied by SNaPshot mutation detection. Results were correlated with clinical outcome by Cox regression analysis. To assess the predictive power of different predictor subsets to detect high grade and tumor invasion, logistic regression models were learned. Additionally, voided urine samples of 119 patients were investigated. After cytologic examination, urine samples were matched with their biopsies and analyzed for loss of heterozygosity (LOH), FGFR3 mutation, polysomy, and p16 deletion using UroVysion FISH. Receiver operator characteristic curves for various predictor subsets were plotted.
    Results: In biopsies, high grade and solid growth pattern were independent prognostic factors for overall survival. A model consisting of UroVysion FISH and FGFR3 status (FISH + FGFR3) predicted high grade significantly better compared with a recently proposed molecular grade (MIB1 + FGFR3). In voided urine, the combination of cytology with LOH analysis (CYTO + LOH) reached the highest diagnostic accuracy for the detection of bladder cancer cells and performed better than cytology alone (sensitivity of 88.2\% and specificity of 97.1\%).
    Conclusions: The combination of cytology with LOH analysis could reduce unpleasant cystoscopies for bladder cancer patients.},
    number = {6},
    journal = {Cancer Epidemiol Biomarkers Prev},
    author = {Wild, Peter J. and Fuchs, Thomas J. and Stoehr, Robert and Zimmermann, Dieter and Frigerio, Simona and Padberg, Barbara and Steiner, Inbal and Zwarthoff, Ellen C. and Burger, Maximilian and Denzinger, Stefan and Hofstaedter, Ferdinand and Kristiansen, Glen and Hermanns, Thomas and Seifert, Hans-Helge and Provenzano, Maurizio and Sulser, Tullio and Roth, Volker and Buhmann, Joachim M. and Moch, Holger and Hartmann, Arndt},
    year = {2009},
    pages = {1798--1806}
}
Download Endnote/RIS citation
TY - JOUR
TI - Detection of Urothelial Bladder Cancer Cells in Voided Urine Can Be Improved by a Combination of Cytology and Standardized Microsatellite Analysis
AU - Wild, Peter J.
AU - Fuchs, Thomas J.
AU - Stoehr, Robert
AU - Zimmermann, Dieter
AU - Frigerio, Simona
AU - Padberg, Barbara
AU - Steiner, Inbal
AU - Zwarthoff, Ellen C.
AU - Burger, Maximilian
AU - Denzinger, Stefan
AU - Hofstaedter, Ferdinand
AU - Kristiansen, Glen
AU - Hermanns, Thomas
AU - Seifert, Hans-Helge
AU - Provenzano, Maurizio
AU - Sulser, Tullio
AU - Roth, Volker
AU - Buhmann, Joachim M.
AU - Moch, Holger
AU - Hartmann, Arndt
T2 - Cancer Epidemiol Biomarkers Prev
AB - Purpose: To evaluate molecular and immunohistochemical markers to develop a molecular grading of urothelial bladder cancer and to test these markers in voided urine samples.
Experimental Design: 255 consecutive biopsies from primary bladder cancer patients were evaluated on a tissue microarray. The clinical parameters gender, age, adjacent carcinoma in situ, and multifocality were collected. UroVysion fluorescence in situ hybridization (FISH) was done. Expression of cytokeratin 20, MIB1, and TP53 was analyzed by immunohistochemistry. Fibroblast growth factor receptor 3 (FGFR3) status was studied by SNaPshot mutation detection. Results were correlated with clinical outcome by Cox regression analysis. To assess the predictive power of different predictor subsets to detect high grade and tumor invasion, logistic regression models were learned. Additionally, voided urine samples of 119 patients were investigated. After cytologic examination, urine samples were matched with their biopsies and analyzed for loss of heterozygosity (LOH), FGFR3 mutation, polysomy, and p16 deletion using UroVysion FISH. Receiver operator characteristic curves for various predictor subsets were plotted.
Results: In biopsies, high grade and solid growth pattern were independent prognostic factors for overall survival. A model consisting of UroVysion FISH and FGFR3 status (FISH + FGFR3) predicted high grade significantly better compared with a recently proposed molecular grade (MIB1 + FGFR3). In voided urine, the combination of cytology with LOH analysis (CYTO + LOH) reached the highest diagnostic accuracy for the detection of bladder cancer cells and performed better than cytology alone (sensitivity of 88.2% and specificity of 97.1%).
Conclusions: The combination of cytology with LOH analysis could reduce unpleasant cystoscopies for bladder cancer patients.
DA - 2009///
PY - 2009
DO - 10.1158/1055-9965.EPI-09-0099
VL - 18
IS - 6
SP - 1798
EP - 1806
UR - http://cebp.aacrjournals.org/cgi/content/abstract/18/6/1798
ER -
Purpose: To evaluate molecular and immunohistochemical markers to develop a molecular grading of urothelial bladder cancer and to test these markers in voided urine samples. Experimental Design: 255 consecutive biopsies from primary bladder cancer patients were evaluated on a tissue microarray. The clinical parameters gender, age, adjacent carcinoma in situ, and multifocality were collected. UroVysion fluorescence in situ hybridization (FISH) was done. Expression of cytokeratin 20, MIB1, and TP53 was analyzed by immunohistochemistry. Fibroblast growth factor receptor 3 (FGFR3) status was studied by SNaPshot mutation detection. Results were correlated with clinical outcome by Cox regression analysis. To assess the predictive power of different predictor subsets to detect high grade and tumor invasion, logistic regression models were learned. Additionally, voided urine samples of 119 patients were investigated. After cytologic examination, urine samples were matched with their biopsies and analyzed for loss of heterozygosity (LOH), FGFR3 mutation, polysomy, and p16 deletion using UroVysion FISH. Receiver operator characteristic curves for various predictor subsets were plotted. Results: In biopsies, high grade and solid growth pattern were independent prognostic factors for overall survival. A model consisting of UroVysion FISH and FGFR3 status (FISH + FGFR3) predicted high grade significantly better compared with a recently proposed molecular grade (MIB1 + FGFR3). In voided urine, the combination of cytology with LOH analysis (CYTO + LOH) reached the highest diagnostic accuracy for the detection of bladder cancer cells and performed better than cytology alone (sensitivity of 88.2% and specificity of 97.1%). Conclusions: The combination of cytology with LOH analysis could reduce unpleasant cystoscopies for bladder cancer patients.
Prognostic Relevance of Wnt-Inhibitory Factor-1 (WIF1) and Dickkopf-3 (DKK3) Promoter Methylation in Human Breast Cancer.
Jurgen Veeck, Peter Wild, Thomas J. Fuchs, Peter Schueffler, Arndt Hartmann, Ruth Knuchel and Edgar Dahl.
BMC Cancer, vol. 9, 1, p. 217, 2009
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@article{veeck_prognostic_2009,
    title = {Prognostic {Relevance} of {Wnt}-{Inhibitory} {Factor}-1 ({WIF}1) and {Dickkopf}-3 ({DKK}3) {Promoter} {Methylation} in {Human} {Breast} {Cancer}},
    volume = {9},
    issn = {1471-2407},
    url = {http://www.biomedcentral.com/1471-2407/9/217},
    doi = {10.1186/1471-2407-9-217},
    abstract = {Background
    Secreted Wnt signaling antagonists have recently been described as frequent targets of epigenetic inactivation in human tumor entities. Since gene silencing of certain Wnt antagonists was found to be correlated with adverse patient survival in cancer, we aimed at investigating a potential prognostic impact of the two Wnt antagonizing molecules WIF1 and DKK3 in breast cancer, which are frequently silenced by promoter methylation in this disease.
    Methods
    WIF1 and DKK3 promoter methylation were assessed by methylation-specific PCR with bisulfite-converted DNA from 19 normal breast tissues and 150 primary breast carcinomas. Promoter methylation was interpreted in a qualitative, binary fashion. Statistical evaluations included two-sided Fisher's exact tests, univariate log-rank tests of Kaplan-Meier curves as well as multivariate Cox regression analyses.
    Results
    WIF1 and DKK3 promoter methylation were detected in 63.3\% (95/150) and 61.3\% (92/150) of breast carcinoma samples, respectively. In normal breast tissues, WIF1 methylation was present in 0\% (0/19) and DKK3 methylation in 5.3\% (1/19) of samples. In breast carcinomas, WIF1 methylation was significantly associated with methylation of DKK3 (p = 0.009). Methylation of either gene was not associated with clinicopathological parameters, except for DKK3 methylation being associated with patient age (p = 0.007). In univariate analysis, WIF1 methylation was not associated with clinical patient outcome. In contrast, DKK3 methylation was a prognostic factor in patient overall survival (OS) and disease-free survival (DFS). Estimated OS rates after 10 years were 54\% for patients with DKK3 -methylated tumors, in contrast to patients without DKK3 methylation in the tumor, who had a favorable 97\% OS after 10 years (p {\textless} 0.001). Likewise, DFS at 10 years for patients harboring DKK3 methylation in the tumor was 58\%, compared with 78\% for patients with unmethylated DKK3 (p = 0.037). Multivariate analyses revealed that DKK3 methylation was an independent prognostic factor predicting poor OS (hazard ratio (HR): 14.4; 95\% confidence interval (CI): 1.9–111.6; p = 0.011), and short DFS (HR: 2.5; 95\% CI: 1.0–6.0; p = 0.047) in breast cancer.
    Conclusion
    Although the Wnt antagonist genes WIF1 and DKK3 show a very similar frequency of promoter methylation in human breast cancer, only DKK3 methylation proves as a novel prognostic marker potentially useful in the clinical management of this disease.},
    number = {1},
    journal = {BMC Cancer},
    author = {Veeck, Jurgen and Wild, Peter and Fuchs, Thomas J. and Schueffler, Peter and Hartmann, Arndt and Knuchel, Ruth and Dahl, Edgar},
    year = {2009},
    pages = {217}
}
Download Endnote/RIS citation
TY - JOUR
TI - Prognostic Relevance of Wnt-Inhibitory Factor-1 (WIF1) and Dickkopf-3 (DKK3) Promoter Methylation in Human Breast Cancer
AU - Veeck, Jurgen
AU - Wild, Peter
AU - Fuchs, Thomas J.
AU - Schueffler, Peter
AU - Hartmann, Arndt
AU - Knuchel, Ruth
AU - Dahl, Edgar
T2 - BMC Cancer
AB - Background
Secreted Wnt signaling antagonists have recently been described as frequent targets of epigenetic inactivation in human tumor entities. Since gene silencing of certain Wnt antagonists was found to be correlated with adverse patient survival in cancer, we aimed at investigating a potential prognostic impact of the two Wnt antagonizing molecules WIF1 and DKK3 in breast cancer, which are frequently silenced by promoter methylation in this disease.
Methods
WIF1 and DKK3 promoter methylation were assessed by methylation-specific PCR with bisulfite-converted DNA from 19 normal breast tissues and 150 primary breast carcinomas. Promoter methylation was interpreted in a qualitative, binary fashion. Statistical evaluations included two-sided Fisher's exact tests, univariate log-rank tests of Kaplan-Meier curves as well as multivariate Cox regression analyses.
Results
WIF1 and DKK3 promoter methylation were detected in 63.3% (95/150) and 61.3% (92/150) of breast carcinoma samples, respectively. In normal breast tissues, WIF1 methylation was present in 0% (0/19) and DKK3 methylation in 5.3% (1/19) of samples. In breast carcinomas, WIF1 methylation was significantly associated with methylation of DKK3 (p = 0.009). Methylation of either gene was not associated with clinicopathological parameters, except for DKK3 methylation being associated with patient age (p = 0.007). In univariate analysis, WIF1 methylation was not associated with clinical patient outcome. In contrast, DKK3 methylation was a prognostic factor in patient overall survival (OS) and disease-free survival (DFS). Estimated OS rates after 10 years were 54% for patients with DKK3 -methylated tumors, in contrast to patients without DKK3 methylation in the tumor, who had a favorable 97% OS after 10 years (p < 0.001). Likewise, DFS at 10 years for patients harboring DKK3 methylation in the tumor was 58%, compared with 78% for patients with unmethylated DKK3 (p = 0.037). Multivariate analyses revealed that DKK3 methylation was an independent prognostic factor predicting poor OS (hazard ratio (HR): 14.4; 95% confidence interval (CI): 1.9–111.6; p = 0.011), and short DFS (HR: 2.5; 95% CI: 1.0–6.0; p = 0.047) in breast cancer.
Conclusion
Although the Wnt antagonist genes WIF1 and DKK3 show a very similar frequency of promoter methylation in human breast cancer, only DKK3 methylation proves as a novel prognostic marker potentially useful in the clinical management of this disease.
DA - 2009///
PY - 2009
DO - 10.1186/1471-2407-9-217
VL - 9
IS - 1
SP - 217
SN - 1471-2407
UR - http://www.biomedcentral.com/1471-2407/9/217
ER -
Background Secreted Wnt signaling antagonists have recently been described as frequent targets of epigenetic inactivation in human tumor entities. Since gene silencing of certain Wnt antagonists was found to be correlated with adverse patient survival in cancer, we aimed at investigating a potential prognostic impact of the two Wnt antagonizing molecules WIF1 and DKK3 in breast cancer, which are frequently silenced by promoter methylation in this disease. Methods WIF1 and DKK3 promoter methylation were assessed by methylation-specific PCR with bisulfite-converted DNA from 19 normal breast tissues and 150 primary breast carcinomas. Promoter methylation was interpreted in a qualitative, binary fashion. Statistical evaluations included two-sided Fisher's exact tests, univariate log-rank tests of Kaplan-Meier curves as well as multivariate Cox regression analyses. Results WIF1 and DKK3 promoter methylation were detected in 63.3% (95/150) and 61.3% (92/150) of breast carcinoma samples, respectively. In normal breast tissues, WIF1 methylation was present in 0% (0/19) and DKK3 methylation in 5.3% (1/19) of samples. In breast carcinomas, WIF1 methylation was significantly associated with methylation of DKK3 (p = 0.009). Methylation of either gene was not associated with clinicopathological parameters, except for DKK3 methylation being associated with patient age (p = 0.007). In univariate analysis, WIF1 methylation was not associated with clinical patient outcome. In contrast, DKK3 methylation was a prognostic factor in patient overall survival (OS) and disease-free survival (DFS). Estimated OS rates after 10 years were 54% for patients with DKK3 -methylated tumors, in contrast to patients without DKK3 methylation in the tumor, who had a favorable 97% OS after 10 years (p < 0.001). Likewise, DFS at 10 years for patients harboring DKK3 methylation in the tumor was 58%, compared with 78% for patients with unmethylated DKK3 (p = 0.037). Multivariate analyses revealed that DKK3 methylation was an independent prognostic factor predicting poor OS (hazard ratio (HR): 14.4; 95% confidence interval (CI): 1.9–111.6; p = 0.011), and short DFS (HR: 2.5; 95% CI: 1.0–6.0; p = 0.047) in breast cancer. Conclusion Although the Wnt antagonist genes WIF1 and DKK3 show a very similar frequency of promoter methylation in human breast cancer, only DKK3 methylation proves as a novel prognostic marker potentially useful in the clinical management of this disease.
Nuclear Karyopherin Alpha2 Expression Predicts Poor Survival in Patients with Advanced Breast Cancer Irrespective of Treatment Intensity.
Oleg Gluz, Peter Wild, Robert Meiler, Raihana Diallo-Danebrock, Evelyn Ting, Svjetlana Mohrmann, Gerhart Schuett, Edgar Dahl, Thomas J. Fuchs, Alexander Herr, Andreas Gaumann, Markus Frick, Christopher Poremba, Ulrike Anneliese Nitz and Arndt Hartmann.
International Journal of Cancer, vol. 123/6, IF 4,693, p. 1433–1438, 2008
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@article{gluz_nuclear_2008,
    title = {Nuclear {Karyopherin} {Alpha}2 {Expression} {Predicts} {Poor} {Survival} in {Patients} with {Advanced} {Breast} {Cancer} {Irrespective} of {Treatment} {Intensity}},
    volume = {123/6},
    issn = {1097-0215},
    url = {http://onlinelibrary.wiley.com/doi/10.1002/ijc.23628/full},
    doi = {10.1002/ijc.23628},
    number = {IF 4,693},
    journal = {International Journal of Cancer},
    author = {Gluz, Oleg and Wild, Peter and Meiler, Robert and Diallo-Danebrock, Raihana and Ting, Evelyn and Mohrmann, Svjetlana and Schuett, Gerhart and Dahl, Edgar and Fuchs, Thomas J. and Herr, Alexander and Gaumann, Andreas and Frick, Markus and Poremba, Christopher and Nitz, Ulrike Anneliese and Hartmann, Arndt},
    year = {2008},
    pages = {1433--1438}
}
Download Endnote/RIS citation
TY - JOUR
TI - Nuclear Karyopherin Alpha2 Expression Predicts Poor Survival in Patients with Advanced Breast Cancer Irrespective of Treatment Intensity
AU - Gluz, Oleg
AU - Wild, Peter
AU - Meiler, Robert
AU - Diallo-Danebrock, Raihana
AU - Ting, Evelyn
AU - Mohrmann, Svjetlana
AU - Schuett, Gerhart
AU - Dahl, Edgar
AU - Fuchs, Thomas J.
AU - Herr, Alexander
AU - Gaumann, Andreas
AU - Frick, Markus
AU - Poremba, Christopher
AU - Nitz, Ulrike Anneliese
AU - Hartmann, Arndt
T2 - International Journal of Cancer
DA - 2008///
PY - 2008
DO - 10.1002/ijc.23628
VL - 123/6
IS - IF 4,693
SP - 1433
EP - 1438
SN - 1097-0215
UR - http://onlinelibrary.wiley.com/doi/10.1002/ijc.23628/full
ER -
The Acute Coronary Syndrome – Pre-Hospital Diagnostic Quality.
Geza Gemes, Thomas J. Fuchs, Gernot Wildner, Freyja-Maria Smolle-Juettner, Josef Smolle, Kurt Stoschitzky and Gerhard Prause.
Resuscitation, vol. 66, 3, p. 323 - 330, 2005
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@article{gemes_acute_2005,
    title = {The {Acute} {Coronary} {Syndrome} – {Pre}-{Hospital} {Diagnostic} {Quality}},
    volume = {66},
    issn = {0300-9572},
    url = {http://www.sciencedirect.com/science/article/B6T19-4GV9846-3/2/bcd3755266ba68b84536b39803426401},
    doi = {DOI: 10.1016/j.resuscitation.2005.04.006},
    abstract = {Background and objective: In the Austrian emergency medical service (EMS), emergency medical technician-staffed and physician-staffed vehicles are in operation. Patients with suspected acute coronary syndromes (ACS) are treated in the pre-hospital phase and transported to the hospital by an emergency physician (EP). This study evaluates the diagnostic performance of EPs in ACS and the impact of this emergency system on the outcome of ACS in an urban area.
    Design: Retrospective case control study.
    Methods: All protocol sheets from the emergency physicians were searched for the diagnosis of ACS. The database of the emergency department (ED) was searched for patients with ACS as an admission diagnosis or ACS as discharge diagnosis. For patients admitted to an intensive care unit (ICU), the medical history from the ICU was reviewed. According to the diagnosis and the aggressiveness of therapy, patients were divided in five categories of severity at each stage of care (pre-hospital category, ED category, ICU category).
    Results: A total of 3585 patients was analysed. Only 17.8\% of the patients with ACS as the admission diagnosis and 20.3\% of the patients with ACS as the discharge diagnosis were transported by an EP. 46.8\% of the ACS diagnosis by EPs were confirmed in hospital. Patients transported by EPs showed a higher all-cause mortality in hospital (1.6\% vs. 0.6\%; p = 0.011). There was no significant correlation between the pre-hospital category of patients treated by EPs and the ED category. When a 12-lead-electrocardiogramm was recorded, the correlation improved slightly (rho: 0.139; p = 0.006).
    Conclusions: The percentage of ACS patients transported to hospital by an EP is very low, and EPs seem to be “over-aware” in the diagnosis of ACS.},
    number = {3},
    journal = {Resuscitation},
    author = {Gemes, Geza and Fuchs, Thomas J. and Wildner, Gernot and Smolle-Juettner, Freyja-Maria and Smolle, Josef and Stoschitzky, Kurt and Prause, Gerhard},
    year = {2005},
    pages = {323 -- 330}
}
Download Endnote/RIS citation
TY - JOUR
TI - The Acute Coronary Syndrome – Pre-Hospital Diagnostic Quality
AU - Gemes, Geza
AU - Fuchs, Thomas J.
AU - Wildner, Gernot
AU - Smolle-Juettner, Freyja-Maria
AU - Smolle, Josef
AU - Stoschitzky, Kurt
AU - Prause, Gerhard
T2 - Resuscitation
AB - Background and objective: In the Austrian emergency medical service (EMS), emergency medical technician-staffed and physician-staffed vehicles are in operation. Patients with suspected acute coronary syndromes (ACS) are treated in the pre-hospital phase and transported to the hospital by an emergency physician (EP). This study evaluates the diagnostic performance of EPs in ACS and the impact of this emergency system on the outcome of ACS in an urban area.
Design: Retrospective case control study.
Methods: All protocol sheets from the emergency physicians were searched for the diagnosis of ACS. The database of the emergency department (ED) was searched for patients with ACS as an admission diagnosis or ACS as discharge diagnosis. For patients admitted to an intensive care unit (ICU), the medical history from the ICU was reviewed. According to the diagnosis and the aggressiveness of therapy, patients were divided in five categories of severity at each stage of care (pre-hospital category, ED category, ICU category).
Results: A total of 3585 patients was analysed. Only 17.8% of the patients with ACS as the admission diagnosis and 20.3% of the patients with ACS as the discharge diagnosis were transported by an EP. 46.8% of the ACS diagnosis by EPs were confirmed in hospital. Patients transported by EPs showed a higher all-cause mortality in hospital (1.6% vs. 0.6%; p = 0.011). There was no significant correlation between the pre-hospital category of patients treated by EPs and the ED category. When a 12-lead-electrocardiogramm was recorded, the correlation improved slightly (rho: 0.139; p = 0.006).
Conclusions: The percentage of ACS patients transported to hospital by an EP is very low, and EPs seem to be “over-aware” in the diagnosis of ACS.
DA - 2005///
PY - 2005
DO - DOI: 10.1016/j.resuscitation.2005.04.006
VL - 66
IS - 3
SP - 323
EP - 330
SN - 0300-9572
UR - http://www.sciencedirect.com/science/article/B6T19-4GV9846-3/2/bcd3755266ba68b84536b39803426401
ER -
Background and objective: In the Austrian emergency medical service (EMS), emergency medical technician-staffed and physician-staffed vehicles are in operation. Patients with suspected acute coronary syndromes (ACS) are treated in the pre-hospital phase and transported to the hospital by an emergency physician (EP). This study evaluates the diagnostic performance of EPs in ACS and the impact of this emergency system on the outcome of ACS in an urban area. Design: Retrospective case control study. Methods: All protocol sheets from the emergency physicians were searched for the diagnosis of ACS. The database of the emergency department (ED) was searched for patients with ACS as an admission diagnosis or ACS as discharge diagnosis. For patients admitted to an intensive care unit (ICU), the medical history from the ICU was reviewed. According to the diagnosis and the aggressiveness of therapy, patients were divided in five categories of severity at each stage of care (pre-hospital category, ED category, ICU category). Results: A total of 3585 patients was analysed. Only 17.8% of the patients with ACS as the admission diagnosis and 20.3% of the patients with ACS as the discharge diagnosis were transported by an EP. 46.8% of the ACS diagnosis by EPs were confirmed in hospital. Patients transported by EPs showed a higher all-cause mortality in hospital (1.6% vs. 0.6%; p = 0.011). There was no significant correlation between the pre-hospital category of patients treated by EPs and the ED category. When a 12-lead-electrocardiogramm was recorded, the correlation improved slightly (rho: 0.139; p = 0.006). Conclusions: The percentage of ACS patients transported to hospital by an EP is very low, and EPs seem to be “over-aware” in the diagnosis of ACS.
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