@phdthesis{Kunz2020,
  author    = {Kunz, Jessica},
  title     = {Kopforthesentherapie bei Patienten mit lagerungsbedingtem Plagiozephalus: Einfluss von Alter und Schweregrad der Asymmetrie bei Therapiebeginn auf die Therapiedauer und das Therapieergebnis},
  doi       = {10.25972/OPUS-20844},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208446},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Zur Kopforthesentherapie in der Behandlung von S{\"a}uglingen mit lagerungsbedingten Sch{\"a}delasymmetrien gibt es bisher kaum Studien, die den optimalen Behandlungsbeginn unter Ber{\"u}cksichtigung der Auspr{\"a}gung der Asymmetrie untersuchen. Ziel der vorliegenden Studie war es daher, den Einfluss des Alters und des Schweregrades der Asymmetrie bei Therapiebeginn auf die Therapiedauer und das Therapieergebnis zu analysieren. Hierzu wurden 144 Patienten mit lagerungsbedingtem Plagiozephalus untersucht, die mittels Kopforthese behandelt wurden. Es erfolgte eine Einteilung in drei Altersgruppen (Altersgruppe I: < 24 Wochen mit N = 38 S{\"a}uglingen / Altersgruppe II: ≥ 24 bis < 32 Wochen mit N = 79 S{\"a}uglingen / Altersgruppe III: ≥ 32 Wochen mit N = 27 S{\"a}uglingen) und je zwei Schweregrade (mild-to-moderate: 30°-CVA >3mm bis <12mm / moderate-to-severe: 30°-CVA ≥12mm). Anhand stereophotogrammetrischer Datens{\"a}tze wurden das Ausmaß und die Reduktion der Asymmetrie in den verschiedenen Untergruppen sowie die Therapiedauer miteinander verglichen. Es zeigte sich, dass es in allen Altersgruppen zu einer signifikanten Reduktion der Asymmetrie kam, wobei sich dieser Effekt mit steigendem Alter verringerte. Ein Therapieerfolg (= CVAI <3,5\%) wurde bei Patienten mit mild-to-moderate Asymmetrie in Altersgruppe I zu 83\%, in Altersgruppe II zu 69\% und in Altersgruppe III zu 40\% erreicht. Bei Patienten mit einer schwerwiegenderen, moderate-to-severe Asymmetrie ergab sich eine symmetrische Kopfform zu 50\% in Altersgruppe I, zu 30\% in Altersgruppe II und nur zu 7\% in Altersgruppe III. Die durchschnittliche Therapiedauer stieg von 18,6 Wochen in Altersgruppe I, 20,0 Wochen in Altersgruppe II und 25,3 Wochen in Altersgruppe III an. Das Alter bzw. der Schweregrad der Asymmetrie bei Behandlungsbeginn wurden durch die multiple Regressionsgleichung ins Verh{\"a}ltnis gesetzt. Dadurch kann zuk{\"u}nftig die zu erwartende Verbesserung der Asymmetrie durch eine Kopforthesentherapie abgesch{\"a}tzt werden. Zusammenfassend kann somit festgestellt werden, dass das Alter bei Therapiebeginn sowie der Auspr{\"a}gungsgrad einer lagerungsbedingten Asymmetrie einen entscheidenden Einfluss auf Dauer und Effektivit{\"a}t der Kopforthesentherapie haben. Die Erfolgsrate der Therapie ist maßgeblich von diesen beiden Einflussfaktoren abh{\"a}ngig. Die aufgestellte Regressionsgleichung erm{\"o}glicht eine Vorhersage der Reduktion einer lagerungsbedingten Sch{\"a}delasymmetrie.},
  subject      = {Kopforthesentherapie},
  language  = {de}
}
@article{EffenbergerBommertKunzetal.2017,
  author    = {Effenberger, Madlen and Bommert, Kathryn S. and Kunz, Viktoria and Kruk, Jessica and Leich, Ellen and Rudelius, Martina and Bargou, Ralf and Bommert, Kurt},
  title     = {Glutaminase inhibition in multiple myeloma induces apoptosis via MYC degradation},
  series = {Oncotarget},
  volume    = {8},
  journal   = {Oncotarget},
  number    = {49},
  doi       = {10.18632/oncotarget.20691},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170168},
  pages     = {85858-85867},
  year      = {2017},
  abstract  = {Multiple Myeloma (MM) is an incurable hematological malignancy affecting millions of people worldwide. As in all tumor cells both glucose and more recently glutamine have been identified as important for MM cellular metabolism, however there is some dispute as to the role of glutamine in MM cell survival. Here we show that the small molecule inhibitor compound 968 effectively inhibits glutaminase and that this inhibition induces apoptosis in both human multiple myeloma cell lines (HMCLs) and primary patient material. The HMCL U266 which does not express MYC was insensitive to both glutamine removal and compound 968, but ectopic expression of MYC imparted sensitivity. Finally, we show that glutamine depletion is reflected by rapid loss of MYC protein which is independent of MYC transcription and post translational modifications. However, MYC loss is dependent on proteasomal activity, and this loss was paralleled by an equally rapid induction of apoptosis. These findings are in contrast to those of glucose depletion which largely affected rates of proliferation in HMCLs, but had no effects on either MYC expression or viability. Therefore, inhibition of glutaminolysis is effective at inducing apoptosis and thus serves as a possible therapeutic target in MM.},
  language  = {en}
}
@article{KunzBommertKruketal.2020,
  author    = {Kunz, Viktoria and Bommert, Kathryn S. and Kruk, Jessica and Schwinning, Daniel and Chatterjee, Manik and St{\"u}hmer, Thorsten and Bargou, Ralf and Bommert, Kurt},
  title     = {Targeting of the E3 ubiquitin-protein ligase HUWE1 impairs DNA repair capacity and tumor growth in preclinical multiple myeloma models},
  series = {Scientific Reports},
  volume    = {10},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-020-75499-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230632},
  year      = {2020},
  abstract  = {Experimental evidence suggests that ubiquitin-protein ligases regulate a number of cellular processes involved in tumorigenesis. We analysed the role of the E3 ubiquitin-protein ligase HUWE1 for pathobiology of multiple myeloma (MM), a still incurable blood cancer. mRNA expression analysis indicates an increase in HUWE1 expression levels correlated with advanced stages of myeloma. Pharmacologic as well as RNAi-mediated HUWE1 inhibition caused anti-proliferative effects in MM cell lines in vitro and in an MM1.S xenotransplantation mouse model. Cell cycle analysis upon HUWE1 inhibition revealed decreased S phase cell fractions. Analyses of potential HUWE1-dependent molecular functions did not show involvement in MYC-dependent gene regulation. However, HUWE1 depleted MM cells displayed increased DNA tail length by comet assay, as well as changes in the levels of DNA damage response mediators such as pBRCA1, DNA-polymerase beta, gamma H2AX and Mcl-1. Our finding that HUWE1 might thus be involved in endogenous DNA repair is further supported by strongly enhanced apoptotic effects of the DNA-damaging agent melphalan in HUWE1 depleted cells in vitro and in vivo. These data suggest that HUWE1 might contribute to tumour growth by endogenous repair of DNA, and could therefore potentially be exploitable in future treatment developments.},
  language  = {en}
}
@article{KannKunzHansenetal.2020,
  author    = {Kann, Simone and Kunz, Meik and Hansen, Jessica and Sievertsen, J{\"u}rgen and Crespo, Jose J. and Loperena, Aristides and Arriens, Sandra and Dandekar, Thomas},
  title     = {Chagas disease: detection of Trypanosoma cruzi by a new, high-specific real time PCR},
  series = {Journal of Clinical Medicine},
  volume    = {9},
  journal   = {Journal of Clinical Medicine},
  number    = {5},
  issn      = {2077-0383},
  doi       = {10.3390/jcm9051517},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205746},
  year      = {2020},
  abstract  = {Background: Chagas disease (CD) is a major burden in Latin America, expanding also to non-endemic countries. A gold standard to detect the CD causing pathogen Trypanosoma cruzi is currently not available. Existing real time polymerase chain reactions (RT-PCRs) lack sensitivity and/or specificity. We present a new, highly specific RT-PCR for the diagnosis and monitoring of CD. Material and Methods: We analyzed 352 serum samples from Indigenous people living in high endemic CD areas of Colombia using three leading RT-PCRs (k-DNA-, TCZ-, 18S rRNA-PCR), the newly developed one (NDO-PCR), a Rapid Test/enzyme-linked immuno sorbent assay (ELISA), and immunofluorescence. Eighty-seven PCR-products were verified by sequence analysis after plasmid vector preparation. Results: The NDO-PCR showed the highest sensitivity (92.3\%), specificity (100\%), and accuracy (94.3\%) for T. cruzi detection in the 87 sequenced samples. Sensitivities and specificities of the kDNA-PCR were 89.2\%/22.7\%, 20.5\%/100\% for TCZ-PCR, and 1.5\%/100\% for the 18S rRNA-PCR. The kDNA-PCR revealed a 77.3\% false positive rate, mostly due to cross-reactions with T. rangeli (NDO-PCR 0\%). TCZ- and 18S rRNA-PCR showed a false negative rate of 79.5\% and 98.5\% (NDO-PCR 7.7\%), respectively. Conclusions: The NDO-PCR demonstrated the highest specificity, sensitivity, and accuracy compared to leading PCRs. Together with serologic tests, it can be considered as a reliable tool for CD detection and can improve CD management significantly.},
  language  = {en}
}