@article{WeisSchoenVictoretal.2011,
  author    = {Weis, Eva and Schoen, Holger and Victor, Anja and Spix, Claudia and Ludwig, Marco and Schneider-Raetzke, Brigitte and Kohlschmidt, Nicolai and Bartsch, Oliver and Gerhold-Ay, Aslihan and Boehm, Nils and Grus, Franz and Haaf, Thomas and Galetzka, Danuta},
  title     = {Reduced mRNA and Protein Expression of the Genomic Caretaker RAD9A in Primary Fibroblasts of Individuals with Childhood and Independent Second Cancer},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {10},
  doi       = {10.1371/journal.pone.0025750},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141838},
  pages     = {e25750},
  year      = {2011},
  abstract  = {Background: The etiology of secondary cancer in childhood cancer survivors is largely unclear. Exposure of normal somatic cells to radiation and/or chemotherapy can damage DNA and if not all DNA lesions are properly fixed, the mis-repair may lead to pathological consequences. It is plausible to assume that genetic differences, i.e. in the pathways responsible for cell cycle control and DNA repair, play a critical role in the development of secondary cancer. Methodology/Findings: To identify factors that may influence the susceptibility for second cancer formation, we recruited 20 individuals who survived a childhood malignancy and then developed a second cancer as well as 20 carefully matched control individuals with childhood malignancy but without a second cancer. By antibody microarrays, we screened primary fibroblasts of matched patients for differences in the amount of representative DNA repair-associated proteins. We found constitutively decreased levels of RAD9A and several other DNA repair proteins in two-cancer patients, compared to one-cancer patients. The RAD9A protein level increased in response to DNA damage, however to a lesser extent in the two-cancer patients. Quantification of mRNA expression by real-time RT PCR revealed lower RAD9A mRNA levels in both untreated and 1 Gy gamma-irradiated cells of two-cancer patients. Conclusions/Significance: Collectively, our results support the idea that modulation of RAD9A and other cell cycle arrest and DNA repair proteins contribute to the risk of developing a second malignancy in childhood cancer patients.},
  language  = {en}
}
@article{WeisSchoenVictoretal.2011,
  author    = {Weis, Eva and Schoen, Holger and Victor, Anja and Spix, Claudia and Ludwig, Marco and Schneider-Raetzke, Brigitte and Kohlschmidt, Nicolai and Bartsch, Oliver and Gerhold-Ay, Aslihan and Boehm, Nils and Grus, Franz and Haaf, Thomas and Galetzka, Danuta},
  title     = {Reduced mRNA and Protein Expression of the Genomic Caretaker RAD9A in Primary Fibroblasts of Individuals with Childhood and Independent Second Cancer},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-74777},
  year      = {2011},
  abstract  = {Background: The etiology of secondary cancer in childhood cancer survivors is largely unclear. Exposure of normal somatic cells to radiation and/or chemotherapy can damage DNA and if not all DNA lesions are properly fixed, the mis-repair may lead to pathological consequences. It is plausible to assume that genetic differences, i.e. in the pathways responsible for cell cycle control and DNA repair, play a critical role in the development of secondary cancer. Methodology/Findings: To identify factors that may influence the susceptibility for second cancer formation, we recruited 20 individuals who survived a childhood malignancy and then developed a second cancer as well as 20 carefully matched control individuals with childhood malignancy but without a second cancer. By antibody microarrays, we screened primary fibroblasts of matched patients for differences in the amount of representative DNA repair-associated proteins. We found constitutively decreased levels of RAD9A and several other DNA repair proteins in two-cancer patients, compared to onecancer patients. The RAD9A protein level increased in response to DNA damage, however to a lesser extent in the twocancer patients. Quantification of mRNA expression by real-time RT PCR revealed lower RAD9A mRNA levels in both untreated and 1 Gy c-irradiated cells of two-cancer patients. Conclusions/Significance: Collectively, our results support the idea that modulation of RAD9A and other cell cycle arrest and DNA repair proteins contribute to the risk of developing a second malignancy in childhood cancer patients.},
  subject      = {Medizin},
  language  = {en}
}
@article{GaletzkaHansmannElHajjetal.2012,
  author    = {Galetzka, Danuta and Hansmann, Tamara and El Hajj, Nady and Weis, Eva and Irmscher, Benjamin and Ludwig, Marco and Schneider-R{\"a}tzke, Brigitte and Kohlschmidt, Nicolai and Beyer, Vera and Bartsch, Oliver and Zechner, Ulrich and Spix, Claudia and Haaf, Thomas},
  title     = {Monozygotic twins discordant for constitutive BRCA1 promoter methylation, childhood cancer and secondary cancer},
  series = {Epigenetics},
  volume    = {7},
  journal   = {Epigenetics},
  number    = {1},
  doi       = {10.4161/epi.7.1.18814},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125386},
  pages     = {47-54},
  year      = {2012},
  abstract  = {We describe monozygotic twins discordant for childhood leukemia and secondary thyroid carcinoma. We used bisulfite pyrosequencing to compare the constitutive promoter methylation of BRCA1 and several other tumor suppressor genes in primary fibroblasts. The affected twin displayed an increased BRCA1 methylation (12\%), compared with her sister (3\%). Subsequent bisulfite plasmid sequencing demonstrated that 13\% (6 of 47) BRCA1 alleles were fully methylated in the affected twin, whereas her sister displayed only single CpG errors without functional implications. This between-twin methylation difference was also found in irradiated fibroblasts and untreated saliva cells. The BRCA1 epimutation may have originated by an early somatic event in the affected twin: approximately 25\% of her body cells derived from different embryonic cell lineages carry one epigenetically inactivated BRCA1 allele. This epimutation was associated with reduced basal protein levels and a higher induction of BRCA1 after DNA damage. In addition, we performed a genome-wide microarray analysis of both sisters and found several copy number variations, i.e., heterozygous deletion and reduced expression of the RSPO3 gene in the affected twin. This monozygotic twin pair represents an impressive example of epigenetic somatic mosaicism, suggesting a role for constitutive epimutations, maybe along with de novo genetic alterations in recurrent tumor development.},
  language  = {en}
}
@phdthesis{Thomas2013,
  author    = {Thomas, Nicolai},
  title     = {Einfluss der EKG-Telemetrie auf die strukturellen Abl{\"a}ufe im Herzinfarktnetz Mainfranken bei der Versorgung von Patienten mit ST-Streckenhebungsmyokardinfarkt (STEMI)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-83769},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Beim akuten Herzinfarkt betr{\"a}gt die 30-Tages-Mortalit{\"a}t immer noch rund 50\%. Die H{\"a}lfte dieser Todesf{\"a}lle geschieht in den ersten 2 Stunden nach Symptombeginn. Zielf{\"u}hrend in der Therapie ist die schnelle Wiederer{\"o}ffnung der verschlossenen Coronararterie. Die Leitlinien der ESC (European Society of Cardiology) empfehlen die prim{\"a}re perkutane Coronarintervention (PPCI) in einem Zeitfenster von weniger als 120 bzw. 90 Minuten nach first medical contact (FMC) durchzuf{\"u}hren. Eine Optimierung der akuten Infarktversorgung erscheint vor diesem Hintergrund dringend erforderlich. Prim{\"a}re Zielgr{\"o}ße des Projekts ist die Verk{\"u}rzung der Contact-to-ballon-Zeit (C2B), also die Zeit zwischen FMC bis zur Ballondilatation. Voraussetzung f{\"u}r schnelle Reaktionszeiten und damit auch f{\"u}r schnelle C2B-Zeiten ist eine sichere und schnelle EKG-Diagnose bereits am pr{\"a}klinischen Einsatzort. Aber, Unsicherheiten bei der STEMI-Diagnostik sind gegenw{\"a}rtig. Um eine Verbesserung der STEMI-Versorgung zu gew{\"a}hrleisten, wurde im Herzinfarktnetz Mainfranken die telemetrische 12-Kanal-EKG-{\"U}bertragung im Pilotversuch eingef{\"u}hrt. In der vorliegenden Arbeit wurde mit Hilfe eines prospektiv erhobenen Patientenregisters untersucht, welchen Einfluss die Etablierung telemetrischer Verfahren in der Akutversorgung von STEMI-Patienten hat. Sowohl die strukturellen Abl{\"a}ufe im Rahmen des Herzinfarktnetzwerkes als auch der klinische Outcome der Patienten wurden untersucht und dokumentiert. Insgesamt erf{\"u}llten {\"u}ber sechs Studienquartale (vom 01.01.2009 bis 30.09.2010) hinweg 310 Patienten die Einschlusskriterien. Die Ergebnisse zeigen, dass durch eine sichere, pr{\"a}klinische EKG-Diagnose mit Hilfe telemetrischer Verfahren, die C2B-Intervalle im Studienzeitraum signifikant reduziert wurden. Auch die innerklinische Behandlung wurde merklich beschleunigt. Zusammenfassend k{\"o}nnen mit Hilfe der telemetrischen EKG-{\"U}bertragung vier wesentliche Punkte verbessert werden. 1. die sichere Diagnosestellung des STEMI; 2. der gezielte Prim{\"a}rtransport in das n{\"a}chstgelegene, geeignete Interventionszentrum; 3. das organsierte Bypassing der n{\"a}chstgelegenen Nicht-Interventionsklinik und somit die Vermeidung von Sekund{\"a}rtransporten; 4. das Bypassing der Notaufnahme und der Intensivstation der Interventionsklinik und somit die Direkt{\"u}bergabe im HKL.},
  subject      = {Herzinfarkt},
  language  = {de}
}