@article{DjuzenovaZimmermannKatzeretal.2015, author = {Djuzenova, Cholpon S. and Zimmermann, Marcus and Katzer, Astrid and Fiedler, Vanessa and Distel, Luitpold V. and Gasser, Martin and Waaga-Gasser, Anna-Maria and Flentje, Michael and Polat, B{\"u}lent}, title = {A prospective study on histone γ-H2AX and 53BP1 foci expression in rectal carcinoma patients: correlation with radiation therapy-induced outcome}, series = {BMC Cancer}, volume = {15}, journal = {BMC Cancer}, number = {856}, doi = {10.1186/s12885-015-1890-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125303}, year = {2015}, abstract = {Background The prognostic value of histone γ-H2AX and 53BP1 proteins to predict the radiotherapy (RT) outcome of patients with rectal carcinoma (RC) was evaluated in a prospective study. High expression of the constitutive histone γ-H2AX is indicative of defective DNA repair pathway and/or genomic instability, whereas 53BP1 (p53-binding protein 1) is a conserved checkpoint protein with properties of a DNA double-strand breaks sensor. Methods Using fluorescence microscopy, we assessed spontaneous and radiation-induced foci of γ-H2AX and 53BP1 in peripheral blood mononuclear cells derived from unselected RC patients (n = 53) undergoing neoadjuvant chemo- and RT. Cells from apparently healthy donors (n = 12) served as references. Results The γ-H2AX assay of in vitro irradiated lymphocytes revealed significantly higher degree of DNA damage in the group of unselected RC patients with respect to the background, initial (0.5 Gy, 30 min) and residual (0.5 Gy and 2 Gy, 24 h post-radiation) damage compared to the control group. Likewise, the numbers of 53BP1 foci analyzed in the samples from 46 RC patients were significantly higher than in controls except for the background DNA damage. However, both markers were not able to predict tumor stage, gastrointestinal toxicity or tumor regression after curative RT. Interestingly, the mean baseline and induced DNA damage was found to be lower in the group of RC patients with tumor stage IV (n = 7) as compared with the stage III (n = 35). The difference, however, did not reach statistical significance, apparently, because of the limited number of patients. Conclusions The study shows higher expression of γ-H2AX and 53BP1 foci in rectal cancer patients compared with healthy individuals. Yet the data in vitro were not predictive in regard to the radiotherapy outcome.}, language = {en} } @article{DjuzenovaElsnerKatzeretal.2013, author = {Djuzenova, Cholpon S. and Elsner, Ines and Katzer, Astrid and Worschech, Eike and Distel, Luitpold V. and Flentje, Michael and Polat, B{\"u}lent}, title = {Radiosensitivity in breast cancer assessed by the histone γ-H2AX and 53BP1 foci}, series = {Radiation Oncology}, journal = {Radiation Oncology}, doi = {10.1186/1748-717X-8-98}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96110}, year = {2013}, abstract = {Background High expression of constitutive histone γ-H2AX, a sensitive marker of DNA damage, might be indicative of defective DNA repair pathway or genomic instability. 53BP1 (p53-binding protein 1) is a conserved checkpoint protein with properties of a DNA double-strand breaks sensor. This study explores the relationship between the clinical radiosensitivity of tumor patients and the expression/induction of γ-H2AX and 53BP1 in vitro. Methods Using immunostaining, we assessed spontaneous and radiation-induced foci of γ-H2AX and 53 BP1 in peripheral blood mononuclear cells derived from unselected breast cancer (BC) patients (n=57) undergoing radiotherapy (RT). Cells from apparently healthy donors (n=12) served as references. Results Non-irradiated cells from controls and unselected BC patients exhibited similar baseline levels of DNA damage assessed by γ-H2AX and 53BP1 foci. At the same time, the γ-H2AX assay of in vitro irradiated cells revealed significant differences between the control group and the group of unselected BC patients with respect to the initial (0.5 Gy, 30 min) and residual (2 Gy, 24 h post-radiation) DNA damage. The numbers of 53BP1 foci analyzed in 35 BC patients were significantly higher than in controls only in case of residual DNA damage. A weak correlation was found between residual foci of both proteins tested. In addition, cells from cancer patients with an adverse acute skin reaction (grade 3) to RT showed significantly increased radiation-induced γ-H2AX foci and their protracted disappearance compared to the group of BC patients with normal skin reaction (grade 0-1). The mean number of γ-H2AX foci after 5 clinical fractions was significantly higher than that before RT, especially in clinically radiosensitive patients. Conclusions The γ-H2AX assay may have potential for screening individual radiosensitivity of breast cancer patients.}, subject = {DNS-Sch{\"a}digung}, language = {en} }