Anna Hester - Academia.edu (original) (raw)
Papers by Anna Hester
InFo Hämatologie + Onkologie
Geburtshilfe und Frauenheilkunde
Introduction With the introduction of the first trastuzumab biosimilar in the summer of 2018, bio... more Introduction With the introduction of the first trastuzumab biosimilar in the summer of 2018, biosimilar antibodies for breast cancer have found their way into the area of gynaecological oncology. The switch of anti-human epidermal growth factor receptor 2 (HER2) therapy from the reference drug Herceptin® to a biosimilar has presented challenges to the clinics. In addition to structural and organisational measures, training of employees as well as patient briefing and acceptance were major challenges. The study presented here records – within the context of quality assurance – how the switch to a trastuzumab biosimilar was implemented at four Bavarian university clinics in the Purchasing Association of Bavarian University Pharmacies. Materials/Methods Questionnaires on treatment figures and the switching process were sent to breast centres and pharmacies of four Bavarian university clinics between July and December 2019. The neoadjuvant, adjuvant and metastasised anti-HER2 therapy w...
Archives of Gynecology and Obstetrics
Objective Ovarian cancer is the most lethal gynecologic cancer. Resveratrol (RSV) is known to alt... more Objective Ovarian cancer is the most lethal gynecologic cancer. Resveratrol (RSV) is known to alter metabolism in cancer. It affects the nuclear retinoid-X-receptor (RXR), which implies a modulating effect of RXR to gynaecologic cancers. Furthermore, RSV targets Sirtuin1 (Sirt1), a histone deacetylase. Study design 123 tissue samples of patients with serous or mucinous ovarian cancer were examined for expression of Sirt1 and RXR. Ovarian cell lines were treated with RSV and consequences on viability and apoptosis were evaluated. The influence of RSV to Sirt1 and RXR expression was analyzed by western blotting Results A correlation of nuclear Sirt1 and RXRα expression could be detected (p = 0.006). Co-expression of nuclear RXRα and cytoplasmic (p = 0.026) or nuclear (p = 0.041) Sirt1 was associated with significantly increased overall survival in advanced tumour stages. Viability was decreased in all cell lines after stimulation with resveratrol, while cell apoptosis was increased. R...
Translational Oncology, 2021
Background:: Enolase-1, primarily known for its role in glucose metabolism, is overexpressed in v... more Background:: Enolase-1, primarily known for its role in glucose metabolism, is overexpressed in various cancer entities. In contrast its alternative spliced nuclear isoform MBP-1 acts as a tumor suppressor. The aim of this study is to analyze the prognostic impact of Enolase-1/ MBP-1 and its functional significance in epithelial ovarian cancer (EOC). Methods:: By immunohistochemistry, Enolase-1 staining was examined in 156 EOC samples. Evaluation of Enolase-1 staining was conducted in the nucleus and the cytoplasm using the semi-quantitative immunoreactive score. Expression levels were correlated with clinical and pathological parameters as well as with overall survival to assess for prognostic impact. Results:: Cytoplasmic and nuclear Enolase-1 expression did not show a significant difference between the histological subtypes (p = 0.1). High nuclear Enolase-1/ MBP-1 staining negativly correlated with the tumor grading (p < 0.001; Cc = − 0.318). Cytoplasmic Enolase-1 did not correlate with clinicopathological data. Higher nuclear Enolase-1/ MBP-1 staining was detected in low-grade serous cancer cases compared to high-grade ones (median IRS 3 (range 0-8) vs. median IRS 2 (range 0-4), p < 0.001). Nuclear Enolase-1/ MBP-1 expression correlated with the Wnt signaling markers membranous beta-catenin (p = 0.007; Cc = 0.235), serine residue 9-phosphorylated glycogen synthase kinase 3 beta (p < 0.001; Cc = 0.341) and snail/slug (p = 0.004; Cc = − 0.257). High nuclear Enolase-1/ MBP-1 expression was associated with improved overall survival (88.6 vs. 33.1 months, median; p = 0.013). Conclusion:: Additional knowledge of Enolase-1/ MBP-1 as a biomarker and its interactions within the Wnt signaling pathway and epithelial-mesenchymal transition potentially improve the prognosis of therapeutic approaches in EOC.
Scientific Reports, 2022
In recurrent epithelial ovarian cancer (EOC) most patients develop platinum-resistance. On molecu... more In recurrent epithelial ovarian cancer (EOC) most patients develop platinum-resistance. On molecular level the NRF2 pathway, a cellular defense mechanism against reactive oxygen species, is induced. In this study, we investigate AKR1C1/2, target of NRF2, in a well-established EOC collective by immunohistochemistry and in a panel of ovarian cancer cell lines including platinum-resistant clones. The therapeutic effect of carboplatin and MPA as monotherapy or in combination was assessed by functional assays, using OV90 and OV90cp cells. Molecular mechanisms of action of MPA were investigated by NRF2 silencing and AKR activity measurements. Immunohistochemical analysis revealed that AKR1C1/2 is a key player in the development of chemoresistance and an independent indicator for short PFS (23.5 vs. 49.6 months, p = 0.013). Inhibition of AKR1C1/2 by MPA led to a concentration- and time-dependent decline of OV90 viability and to an increased response to CP in vitro. By NRF2 silencing, howev...
MMW - Fortschritte der Medizin, 2021
Das Mammakarzinom ist der häufigste maligne Tumor bei Frauen weltweit. In Deutschland erkran ken... more Das Mammakarzinom ist der häufigste maligne Tumor bei Frauen weltweit. In Deutschland erkran ken jährlich ca. 70.000 Frauen (geschätzt für 2020) neu an einem Mammakarzinom. Es ist zudem die häufigste Krebstodesursache bei Frauen. An einem Ovarialkarzinom erkranken jährlich ca. 7.000 Frauen [1]. Es ist die gynä kologische Krebserkran kung mit der höchsten Mortalität. Für die Entstehung von Brustkrebs werden multi ple molekulare Ereignisse genetischer und epigene tischer Art verantwortlich gemacht. In Familien mit gehäuftem Auftreten von Brustkrebs wurden Familiärer Brustund Eierstockkrebs: Auf was achten, was tun?
J. Univers. Comput. Sci., 1998
The World Wide Web is in constant renovation, with new technologies emerging every day. Most of t... more The World Wide Web is in constant renovation, with new technologies emerging every day. Most of these technologies are still incipient, and there are few de facto standards for this \new Web". There is a need for tools that can run with current standard support, but which are exible and extensible enough to be eventually ported to new APIs and to incorporate new technologies. On the other hand, many Web developers cannot keep pace with the fast track of Web technologies. Therefore, it is important for new tools to be simple enough to be mastered quickly by the average programmer. This paper presents CGILua, a Web development tool that matches these requirements. The paper also discusses why this tool is being adopted in many commercial and academic projects, focusing on issues such as exibility, extensibility, simplicity, and portability.
Diagnostics, 2021
The advent of molecular diagnostics and the rising number of targeted therapies have facilitated ... more The advent of molecular diagnostics and the rising number of targeted therapies have facilitated development of precision oncology for cancer patients. In order to demonstrate its impact for patients with metastatic breast cancer (mBC), we initiated a Molecular Tumor Board (MTB) to provide treatment recommendations for mBC patients who had disease progression under standard treatment. NGS (next generation sequencing) was carried out using the Oncomine multi-gene panel testing system (Ion Torrent). The MTB reviewed molecular diagnostics’ results, relevant tumor characteristics, patient’s course of disease and made personalized treatment and/or diagnostic recommendations for each patient. From May 2017 to December 2019, 100 mBC patients were discussed by the local MTB. A total 72% of the mBC tumors had at least one molecular alteration (median 2 per case, range: 1 to 6). The most frequent genetic changes were found in the following genes: PIK3CA (19%) and TP53 (17%). The MTB rated 53%...
Journal of Reproductive Immunology, 2021
BACKROUND Alterations of DNA accessibility and chromatin structure are associated with diseases. ... more BACKROUND Alterations of DNA accessibility and chromatin structure are associated with diseases. We aimed to investigate epigenetic modifications in preeclampsia (PE), a pregnancy-associated hypertonic disease. Specifically, we addressed histone modification proteins H3K9ac (acetylated lysine 9 of the histone H3) and H3K4me3 (trimethylated lysine 4 of the histone H3) in PE. METHODS We analyzed expression of histone proteins H3K4me3 and H3K9ac in 32 PE and 32 control placentas by immunohistochemistry. Further, we carried out confirmatory western blot analysis of respective proteins in 6 representative placentas. We then applied regression models with additional adjustment for potential confounders. RESULTS Expression of H3K4me3 and H3K9ac is reduced in PE placentas as demonstrated by immunohistochemical stainings and western blot. There are no differences between female and male fetuses in the presence of these histone modifications. H3K4me3 positively correlated with maternal age (r = 0.444, p = 0.034). CONCLUSION Expression of the placental histone proteins H3K4me3 and H3K9ac is reduced in PE, and independent of fetal gender. Our study underlines the involvement of epigenetic changes in the placenta of women suffering from PE.
Cells, 2021
The platelet-activating factor receptor (PAFR) and its ligand (PAF) are important inflammatory me... more The platelet-activating factor receptor (PAFR) and its ligand (PAF) are important inflammatory mediators that are overexpressed in ovarian cancer. The receptor is an important player in ovarian cancer development. In this study, we aimed to evaluate the prognostic value of PAFR in epithelial ovarian cancer (EOC) and the potential use of its antagonist, rupatadine, as an experimental treatment. Tissue microarrays of ovarian cancer patients, most markedly those with a non-mucinous subtype, immunohistochemically overexpressed PAFR. Elevated cytoplasmic PAFR expression was found to significantly and independently impair patients’ overall and recurrence-free survival (OS: median 83.48 vs. 155.03 months; p = 0.022; RFS: median 164.46 vs. 78.03 months; p = 0.015). In vitro, the serous ovarian cancer subtypes especially displayed an elevated PAFR gene and protein expression. siRNA knockdown of PAFR decreased cell proliferation significantly, thus confirming the receptor’s protumorigenic eff...
Histochemistry and Cell Biology, 2020
Prostaglandin induced signalling is involved in different cancers. As previously described, the E... more Prostaglandin induced signalling is involved in different cancers. As previously described, the EP3 receptor expression decreases with increasing stage of cervical intraepithelial lesions (CIN). In addition, in cervical cancer EP3 is an independent prognosticator for overall survival and correlates with FIGO stages. Currently the role of Prostaglandin 2 receptor 2 (EP2) in CIN is unknown. The aim of this study was to analyse the expression of EP2 for potential prognostic value for patients with cervical dysplasia. EP2 expression was analysed by immunohistochemistry in 33 patient samples (CIN1–3) using the immune-reactivity scoring system (IRS). Expression levels were correlated with clinical outcome to analyse prognostic relevance in patients with CIN2. Data analysis was performed using non parametric Kruskal–Wallis and Spearman rank sum test. Cytoplasmic expression levels of EP2 correlated significantly (p < 0.001) with different grades of cervical dysplasia. Median EP2-IRS in C...
International Journal of Molecular Sciences, 2020
The aim of this study was to evaluate the prognostic impact of prostaglandin E2 receptor 3 (EP3) ... more The aim of this study was to evaluate the prognostic impact of prostaglandin E2 receptor 3 (EP3) receptor expression might have on the two different breast cancer entities: multifocal/multicentric versus unifocal. As the prognosis determining aspects, we investigated the overall- and disease-free survival by uni-and multivariate analysis. To underline the study’s conclusion, we additionally considered the histopathological grading and the tumor node metastasis (TNM) staging system. A retrospective statistical analysis was performed on survival related events in a series of 289 sporadic breast cancer (BC) patients treated at the Department of Obstetrics and Gynecology at the Ludwig–Maximillian’s University in Munich between 2000 and 2002. The EP3 receptor expression was analyzed by immunohistochemistry and showed to have a significantly positive association with breast cancer prognosis for both entities, although with major differences. Patients with unifocal BC with EP3 receptor exp...
Journal of Cancer Research and Clinical Oncology, 2020
Purpose Thyroid hormone receptors (THR) have manifold functions and are involved in the carcinoge... more Purpose Thyroid hormone receptors (THR) have manifold functions and are involved in the carcinogenesis of several tumor types. Within this study, we aimed to investigate the expression pattern (nuclear versus cytoplasmic) of the THR alpha and its impact on patients survival in ovarian cancer (OvCa). Methods The presence of the thyroid hormone receptors THRα, THRα1 and − 2 was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC) using semi-quantitative immunoreactivity (IR) scores and correlated with clinical, pathological data, subtype of ovarian cancer, clinical data, staining of 20 already described OvCa marker proteins and overall survival (OS). Results Among all subtypes of OvCa, clear cell carcinomas showed the highest THRα expression. Furthermore, nuclear THRα was associated with a reduced survival in this subtype. However, nuclear expressed THRα1 turned out to be a positive prognosticator for all subtypes of OvCa patients. Nuclear THRα2 is a positive pr...
Histochemistry and Cell Biology, 2020
The vitamin D receptor (VDR), primarily known as a crucial mediator of calcium homeostasis and me... more The vitamin D receptor (VDR), primarily known as a crucial mediator of calcium homeostasis and metabolism, has been shown to play a significant role in various cancer entities. Previous studies have focused on vitamin D and its receptor in gynecological cancers, noting that the receptor is upregulated in epithelial ovarian cancer (EOC). The aim of this study is to analyze the prognostic impact of VDR and its functional significance in ovarian cancer. Through immunohistochemistry, VDR staining was examined in 156 ovarian cancer samples. Evaluation of VDR staining was conducted in the nucleus and the cytoplasm using the semi-quantitative immunoreactive score, and the scores were classified into high- and low-level expressions. Expression levels were correlated with clinical and pathological parameters as well as with overall survival to assess for prognostic impact. Differences in cytoplasmic VDR expression were identified between the histological subtypes (p = 0.001). Serous, clear c...
International Journal of Molecular Sciences, 2020
KLF11 (Krüppel-like factor 11) belongs to the family of Sp1/Krüppel-like zinc finger transcriptio... more KLF11 (Krüppel-like factor 11) belongs to the family of Sp1/Krüppel-like zinc finger transcription factors that play important roles in a variety of cell types and tissues. KLF11 was initially described as a transforming growth factor-beta (TGF-β) inducible immediate early gene (TIEG). KLF11 promotes the effects of TGF-β on cell growth control by influencing the TGFβ–Smads signaling pathway and regulating the transcription of genes that induce either apoptosis or cell cycle arrest. In carcinogenesis, KLF11 can show diverse effects. Its function as a tumor suppressor gene can be suppressed by phosphorylation of its binding domains via oncogenic pathways. However, KLF 11 can itself also show tumor-promoting effects and seems to have a crucial role in the epithelial–mesenchymal transition process. Here, we review the current knowledge about the function of KLF11 in cell growth regulation. We focus on its transcriptional regulatory function and its influence on the TGF-β signaling pathw...
InFo Hämatologie + Onkologie, 2020
* Einschlusskriterien (EK) des Deutschen Konsortiums Familiärer Brust-und Eierstockkrebs (DK-FBEK... more * Einschlusskriterien (EK) des Deutschen Konsortiums Familiärer Brust-und Eierstockkrebs (DK-FBEK) basierend auf der genetischen Analyse von 21.401 Familien; bei Vorliegen eines dieser EK liegt die Wahrscheinlichkeit für den Nachweis einer BRCA1/2-Mutation bei ≥ 10 %. Eine Erfassung möglichst aller Mutationsträgerinnen ist anzustreben. Hierzu sollten geeignete Einschlusskritieren weiter validiert werden und Nutzen und Schaden in Studien erarbeitet werden (inklusive populationsbasierter Untersuchungen); LOE = Level of Evidence; PARPi = Behandlung mit PARP-Inhibitor(en) T1 Empfehlung zur BRCA1/2-Testung der Kommission "Mamma" der Arbeitsgemeinschaft Gynäkologische Onkologie e. V. (AGO) [8]; (Tabelle modifiziert nach [8]).
Background Ovarian cancer is most lethal in comparison to all other gynecological cancer cases. W... more Background Ovarian cancer is most lethal in comparison to all other gynecological cancer cases. Within this study, we aimed to investigate the expression of the thyroid hormone receptor alpha and its influence on patient survival in ovarian cancer (OvCa). Methods The presence of the thyroid hormone receptors THRα, THRα1 and -2 were investigated in 156 ovarian cancer samples using immunohistochemistry (IHC) using semi-quantitative immunoreactivity (IR) scores and correlated to clinical, pathological data, subtype of ovarian cancer, clinical data, staining of 20 already described OvCa marker proteins and overall survival (OS). Results Patients with clear cell OvCa showed the highest THRα expression and nuclear THRα expression is associated with reduced survival in this group. In contrast, nuclear expressed THRα1 is a positive prognosticator for all OvCa patients. Nuclear THRα2 is a positive prognosticator for OvCa patients of the serous subtype. Cytoplasmic expression of THRα2 accompa...
Cancer Management and Research, 2019
Purpose: This study aimed to investigate the potential prognostic impact of nuclear factor erythr... more Purpose: This study aimed to investigate the potential prognostic impact of nuclear factor erythroid 2-related factor 2 (NRF2) and progesterone receptor A (PRA)/progesterone receptor B (PRB) in ovarian cancer patients which might be the rationale for putative new treatment strategies. Patients and methods: The presence of NRF2 and PRA/PRB was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC). Staining of NRF2 and PRA/ PRB was rated using the semi-quantitative immunoreactive score (IR score, Remmele's score) and correlated to clinical and pathological data. NRF2 and PRA/PRB expression were compared with respect to the overall survival (OS). Results: NRF2 staining was different in both, the cytoplasm and nucleus between the histological subtypes (p=0.001 and p=0.02, respectively). There was a significant difference in the PRA expression comparing all histological subtypes (p=0.02). Histological subtypes showed no significant differences in the PRB expression. A strong correlation of cytoplasmic NRF2 and PRA expression was detected (cc=0.247, p=0.003) as well as of cytoplasmic NRF2 and PRB expression (cc=0.25, p=0.003), confirmed by immunofluorescence double staining. Cytoplasmic NRF2 expression was associated with a longer OS (median 50.6 vs 32.5 months; p=0.1) as it was seen for PRA expression (median 63.4 vs 33.1 months; p=0.08), although not statistically significant. In addition, high PRB expression (median 80.4 vs 32.5 months; p=0.04) and concurrent expression of cytoplasmic NRF2 and PRA were associated with a significantly longer OS (median 109.7 vs 30.6 months; p=0.02). The same relationship was also noted for NRF2 and PRB with improved OS for patients expressing both cytoplasmic NRF2 and PRB (median 153.5 vs 30.6 months; p=0.009). Silencing of NFE2L2 induced higher mRNA expression of PGR in the cancer cell line OVCAR3 (p>0.05) confirming genetic interactions of NRF2 and PR. Conclusion: In this study, the combination of cytoplasmic NRF2 and high PRA/PRB expression was demonstrated to be associated with improved overall survival in ovarian cancer patients. Further understanding of interactions within the NRF2/AKR1C1/PR pathway could open new additional therapeutic approaches.
InFo Hämatologie + Onkologie
Geburtshilfe und Frauenheilkunde
Introduction With the introduction of the first trastuzumab biosimilar in the summer of 2018, bio... more Introduction With the introduction of the first trastuzumab biosimilar in the summer of 2018, biosimilar antibodies for breast cancer have found their way into the area of gynaecological oncology. The switch of anti-human epidermal growth factor receptor 2 (HER2) therapy from the reference drug Herceptin® to a biosimilar has presented challenges to the clinics. In addition to structural and organisational measures, training of employees as well as patient briefing and acceptance were major challenges. The study presented here records – within the context of quality assurance – how the switch to a trastuzumab biosimilar was implemented at four Bavarian university clinics in the Purchasing Association of Bavarian University Pharmacies. Materials/Methods Questionnaires on treatment figures and the switching process were sent to breast centres and pharmacies of four Bavarian university clinics between July and December 2019. The neoadjuvant, adjuvant and metastasised anti-HER2 therapy w...
Archives of Gynecology and Obstetrics
Objective Ovarian cancer is the most lethal gynecologic cancer. Resveratrol (RSV) is known to alt... more Objective Ovarian cancer is the most lethal gynecologic cancer. Resveratrol (RSV) is known to alter metabolism in cancer. It affects the nuclear retinoid-X-receptor (RXR), which implies a modulating effect of RXR to gynaecologic cancers. Furthermore, RSV targets Sirtuin1 (Sirt1), a histone deacetylase. Study design 123 tissue samples of patients with serous or mucinous ovarian cancer were examined for expression of Sirt1 and RXR. Ovarian cell lines were treated with RSV and consequences on viability and apoptosis were evaluated. The influence of RSV to Sirt1 and RXR expression was analyzed by western blotting Results A correlation of nuclear Sirt1 and RXRα expression could be detected (p = 0.006). Co-expression of nuclear RXRα and cytoplasmic (p = 0.026) or nuclear (p = 0.041) Sirt1 was associated with significantly increased overall survival in advanced tumour stages. Viability was decreased in all cell lines after stimulation with resveratrol, while cell apoptosis was increased. R...
Translational Oncology, 2021
Background:: Enolase-1, primarily known for its role in glucose metabolism, is overexpressed in v... more Background:: Enolase-1, primarily known for its role in glucose metabolism, is overexpressed in various cancer entities. In contrast its alternative spliced nuclear isoform MBP-1 acts as a tumor suppressor. The aim of this study is to analyze the prognostic impact of Enolase-1/ MBP-1 and its functional significance in epithelial ovarian cancer (EOC). Methods:: By immunohistochemistry, Enolase-1 staining was examined in 156 EOC samples. Evaluation of Enolase-1 staining was conducted in the nucleus and the cytoplasm using the semi-quantitative immunoreactive score. Expression levels were correlated with clinical and pathological parameters as well as with overall survival to assess for prognostic impact. Results:: Cytoplasmic and nuclear Enolase-1 expression did not show a significant difference between the histological subtypes (p = 0.1). High nuclear Enolase-1/ MBP-1 staining negativly correlated with the tumor grading (p < 0.001; Cc = − 0.318). Cytoplasmic Enolase-1 did not correlate with clinicopathological data. Higher nuclear Enolase-1/ MBP-1 staining was detected in low-grade serous cancer cases compared to high-grade ones (median IRS 3 (range 0-8) vs. median IRS 2 (range 0-4), p < 0.001). Nuclear Enolase-1/ MBP-1 expression correlated with the Wnt signaling markers membranous beta-catenin (p = 0.007; Cc = 0.235), serine residue 9-phosphorylated glycogen synthase kinase 3 beta (p < 0.001; Cc = 0.341) and snail/slug (p = 0.004; Cc = − 0.257). High nuclear Enolase-1/ MBP-1 expression was associated with improved overall survival (88.6 vs. 33.1 months, median; p = 0.013). Conclusion:: Additional knowledge of Enolase-1/ MBP-1 as a biomarker and its interactions within the Wnt signaling pathway and epithelial-mesenchymal transition potentially improve the prognosis of therapeutic approaches in EOC.
Scientific Reports, 2022
In recurrent epithelial ovarian cancer (EOC) most patients develop platinum-resistance. On molecu... more In recurrent epithelial ovarian cancer (EOC) most patients develop platinum-resistance. On molecular level the NRF2 pathway, a cellular defense mechanism against reactive oxygen species, is induced. In this study, we investigate AKR1C1/2, target of NRF2, in a well-established EOC collective by immunohistochemistry and in a panel of ovarian cancer cell lines including platinum-resistant clones. The therapeutic effect of carboplatin and MPA as monotherapy or in combination was assessed by functional assays, using OV90 and OV90cp cells. Molecular mechanisms of action of MPA were investigated by NRF2 silencing and AKR activity measurements. Immunohistochemical analysis revealed that AKR1C1/2 is a key player in the development of chemoresistance and an independent indicator for short PFS (23.5 vs. 49.6 months, p = 0.013). Inhibition of AKR1C1/2 by MPA led to a concentration- and time-dependent decline of OV90 viability and to an increased response to CP in vitro. By NRF2 silencing, howev...
MMW - Fortschritte der Medizin, 2021
Das Mammakarzinom ist der häufigste maligne Tumor bei Frauen weltweit. In Deutschland erkran ken... more Das Mammakarzinom ist der häufigste maligne Tumor bei Frauen weltweit. In Deutschland erkran ken jährlich ca. 70.000 Frauen (geschätzt für 2020) neu an einem Mammakarzinom. Es ist zudem die häufigste Krebstodesursache bei Frauen. An einem Ovarialkarzinom erkranken jährlich ca. 7.000 Frauen [1]. Es ist die gynä kologische Krebserkran kung mit der höchsten Mortalität. Für die Entstehung von Brustkrebs werden multi ple molekulare Ereignisse genetischer und epigene tischer Art verantwortlich gemacht. In Familien mit gehäuftem Auftreten von Brustkrebs wurden Familiärer Brustund Eierstockkrebs: Auf was achten, was tun?
J. Univers. Comput. Sci., 1998
The World Wide Web is in constant renovation, with new technologies emerging every day. Most of t... more The World Wide Web is in constant renovation, with new technologies emerging every day. Most of these technologies are still incipient, and there are few de facto standards for this \new Web". There is a need for tools that can run with current standard support, but which are exible and extensible enough to be eventually ported to new APIs and to incorporate new technologies. On the other hand, many Web developers cannot keep pace with the fast track of Web technologies. Therefore, it is important for new tools to be simple enough to be mastered quickly by the average programmer. This paper presents CGILua, a Web development tool that matches these requirements. The paper also discusses why this tool is being adopted in many commercial and academic projects, focusing on issues such as exibility, extensibility, simplicity, and portability.
Diagnostics, 2021
The advent of molecular diagnostics and the rising number of targeted therapies have facilitated ... more The advent of molecular diagnostics and the rising number of targeted therapies have facilitated development of precision oncology for cancer patients. In order to demonstrate its impact for patients with metastatic breast cancer (mBC), we initiated a Molecular Tumor Board (MTB) to provide treatment recommendations for mBC patients who had disease progression under standard treatment. NGS (next generation sequencing) was carried out using the Oncomine multi-gene panel testing system (Ion Torrent). The MTB reviewed molecular diagnostics’ results, relevant tumor characteristics, patient’s course of disease and made personalized treatment and/or diagnostic recommendations for each patient. From May 2017 to December 2019, 100 mBC patients were discussed by the local MTB. A total 72% of the mBC tumors had at least one molecular alteration (median 2 per case, range: 1 to 6). The most frequent genetic changes were found in the following genes: PIK3CA (19%) and TP53 (17%). The MTB rated 53%...
Journal of Reproductive Immunology, 2021
BACKROUND Alterations of DNA accessibility and chromatin structure are associated with diseases. ... more BACKROUND Alterations of DNA accessibility and chromatin structure are associated with diseases. We aimed to investigate epigenetic modifications in preeclampsia (PE), a pregnancy-associated hypertonic disease. Specifically, we addressed histone modification proteins H3K9ac (acetylated lysine 9 of the histone H3) and H3K4me3 (trimethylated lysine 4 of the histone H3) in PE. METHODS We analyzed expression of histone proteins H3K4me3 and H3K9ac in 32 PE and 32 control placentas by immunohistochemistry. Further, we carried out confirmatory western blot analysis of respective proteins in 6 representative placentas. We then applied regression models with additional adjustment for potential confounders. RESULTS Expression of H3K4me3 and H3K9ac is reduced in PE placentas as demonstrated by immunohistochemical stainings and western blot. There are no differences between female and male fetuses in the presence of these histone modifications. H3K4me3 positively correlated with maternal age (r = 0.444, p = 0.034). CONCLUSION Expression of the placental histone proteins H3K4me3 and H3K9ac is reduced in PE, and independent of fetal gender. Our study underlines the involvement of epigenetic changes in the placenta of women suffering from PE.
Cells, 2021
The platelet-activating factor receptor (PAFR) and its ligand (PAF) are important inflammatory me... more The platelet-activating factor receptor (PAFR) and its ligand (PAF) are important inflammatory mediators that are overexpressed in ovarian cancer. The receptor is an important player in ovarian cancer development. In this study, we aimed to evaluate the prognostic value of PAFR in epithelial ovarian cancer (EOC) and the potential use of its antagonist, rupatadine, as an experimental treatment. Tissue microarrays of ovarian cancer patients, most markedly those with a non-mucinous subtype, immunohistochemically overexpressed PAFR. Elevated cytoplasmic PAFR expression was found to significantly and independently impair patients’ overall and recurrence-free survival (OS: median 83.48 vs. 155.03 months; p = 0.022; RFS: median 164.46 vs. 78.03 months; p = 0.015). In vitro, the serous ovarian cancer subtypes especially displayed an elevated PAFR gene and protein expression. siRNA knockdown of PAFR decreased cell proliferation significantly, thus confirming the receptor’s protumorigenic eff...
Histochemistry and Cell Biology, 2020
Prostaglandin induced signalling is involved in different cancers. As previously described, the E... more Prostaglandin induced signalling is involved in different cancers. As previously described, the EP3 receptor expression decreases with increasing stage of cervical intraepithelial lesions (CIN). In addition, in cervical cancer EP3 is an independent prognosticator for overall survival and correlates with FIGO stages. Currently the role of Prostaglandin 2 receptor 2 (EP2) in CIN is unknown. The aim of this study was to analyse the expression of EP2 for potential prognostic value for patients with cervical dysplasia. EP2 expression was analysed by immunohistochemistry in 33 patient samples (CIN1–3) using the immune-reactivity scoring system (IRS). Expression levels were correlated with clinical outcome to analyse prognostic relevance in patients with CIN2. Data analysis was performed using non parametric Kruskal–Wallis and Spearman rank sum test. Cytoplasmic expression levels of EP2 correlated significantly (p < 0.001) with different grades of cervical dysplasia. Median EP2-IRS in C...
International Journal of Molecular Sciences, 2020
The aim of this study was to evaluate the prognostic impact of prostaglandin E2 receptor 3 (EP3) ... more The aim of this study was to evaluate the prognostic impact of prostaglandin E2 receptor 3 (EP3) receptor expression might have on the two different breast cancer entities: multifocal/multicentric versus unifocal. As the prognosis determining aspects, we investigated the overall- and disease-free survival by uni-and multivariate analysis. To underline the study’s conclusion, we additionally considered the histopathological grading and the tumor node metastasis (TNM) staging system. A retrospective statistical analysis was performed on survival related events in a series of 289 sporadic breast cancer (BC) patients treated at the Department of Obstetrics and Gynecology at the Ludwig–Maximillian’s University in Munich between 2000 and 2002. The EP3 receptor expression was analyzed by immunohistochemistry and showed to have a significantly positive association with breast cancer prognosis for both entities, although with major differences. Patients with unifocal BC with EP3 receptor exp...
Journal of Cancer Research and Clinical Oncology, 2020
Purpose Thyroid hormone receptors (THR) have manifold functions and are involved in the carcinoge... more Purpose Thyroid hormone receptors (THR) have manifold functions and are involved in the carcinogenesis of several tumor types. Within this study, we aimed to investigate the expression pattern (nuclear versus cytoplasmic) of the THR alpha and its impact on patients survival in ovarian cancer (OvCa). Methods The presence of the thyroid hormone receptors THRα, THRα1 and − 2 was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC) using semi-quantitative immunoreactivity (IR) scores and correlated with clinical, pathological data, subtype of ovarian cancer, clinical data, staining of 20 already described OvCa marker proteins and overall survival (OS). Results Among all subtypes of OvCa, clear cell carcinomas showed the highest THRα expression. Furthermore, nuclear THRα was associated with a reduced survival in this subtype. However, nuclear expressed THRα1 turned out to be a positive prognosticator for all subtypes of OvCa patients. Nuclear THRα2 is a positive pr...
Histochemistry and Cell Biology, 2020
The vitamin D receptor (VDR), primarily known as a crucial mediator of calcium homeostasis and me... more The vitamin D receptor (VDR), primarily known as a crucial mediator of calcium homeostasis and metabolism, has been shown to play a significant role in various cancer entities. Previous studies have focused on vitamin D and its receptor in gynecological cancers, noting that the receptor is upregulated in epithelial ovarian cancer (EOC). The aim of this study is to analyze the prognostic impact of VDR and its functional significance in ovarian cancer. Through immunohistochemistry, VDR staining was examined in 156 ovarian cancer samples. Evaluation of VDR staining was conducted in the nucleus and the cytoplasm using the semi-quantitative immunoreactive score, and the scores were classified into high- and low-level expressions. Expression levels were correlated with clinical and pathological parameters as well as with overall survival to assess for prognostic impact. Differences in cytoplasmic VDR expression were identified between the histological subtypes (p = 0.001). Serous, clear c...
International Journal of Molecular Sciences, 2020
KLF11 (Krüppel-like factor 11) belongs to the family of Sp1/Krüppel-like zinc finger transcriptio... more KLF11 (Krüppel-like factor 11) belongs to the family of Sp1/Krüppel-like zinc finger transcription factors that play important roles in a variety of cell types and tissues. KLF11 was initially described as a transforming growth factor-beta (TGF-β) inducible immediate early gene (TIEG). KLF11 promotes the effects of TGF-β on cell growth control by influencing the TGFβ–Smads signaling pathway and regulating the transcription of genes that induce either apoptosis or cell cycle arrest. In carcinogenesis, KLF11 can show diverse effects. Its function as a tumor suppressor gene can be suppressed by phosphorylation of its binding domains via oncogenic pathways. However, KLF 11 can itself also show tumor-promoting effects and seems to have a crucial role in the epithelial–mesenchymal transition process. Here, we review the current knowledge about the function of KLF11 in cell growth regulation. We focus on its transcriptional regulatory function and its influence on the TGF-β signaling pathw...
InFo Hämatologie + Onkologie, 2020
* Einschlusskriterien (EK) des Deutschen Konsortiums Familiärer Brust-und Eierstockkrebs (DK-FBEK... more * Einschlusskriterien (EK) des Deutschen Konsortiums Familiärer Brust-und Eierstockkrebs (DK-FBEK) basierend auf der genetischen Analyse von 21.401 Familien; bei Vorliegen eines dieser EK liegt die Wahrscheinlichkeit für den Nachweis einer BRCA1/2-Mutation bei ≥ 10 %. Eine Erfassung möglichst aller Mutationsträgerinnen ist anzustreben. Hierzu sollten geeignete Einschlusskritieren weiter validiert werden und Nutzen und Schaden in Studien erarbeitet werden (inklusive populationsbasierter Untersuchungen); LOE = Level of Evidence; PARPi = Behandlung mit PARP-Inhibitor(en) T1 Empfehlung zur BRCA1/2-Testung der Kommission "Mamma" der Arbeitsgemeinschaft Gynäkologische Onkologie e. V. (AGO) [8]; (Tabelle modifiziert nach [8]).
Background Ovarian cancer is most lethal in comparison to all other gynecological cancer cases. W... more Background Ovarian cancer is most lethal in comparison to all other gynecological cancer cases. Within this study, we aimed to investigate the expression of the thyroid hormone receptor alpha and its influence on patient survival in ovarian cancer (OvCa). Methods The presence of the thyroid hormone receptors THRα, THRα1 and -2 were investigated in 156 ovarian cancer samples using immunohistochemistry (IHC) using semi-quantitative immunoreactivity (IR) scores and correlated to clinical, pathological data, subtype of ovarian cancer, clinical data, staining of 20 already described OvCa marker proteins and overall survival (OS). Results Patients with clear cell OvCa showed the highest THRα expression and nuclear THRα expression is associated with reduced survival in this group. In contrast, nuclear expressed THRα1 is a positive prognosticator for all OvCa patients. Nuclear THRα2 is a positive prognosticator for OvCa patients of the serous subtype. Cytoplasmic expression of THRα2 accompa...
Cancer Management and Research, 2019
Purpose: This study aimed to investigate the potential prognostic impact of nuclear factor erythr... more Purpose: This study aimed to investigate the potential prognostic impact of nuclear factor erythroid 2-related factor 2 (NRF2) and progesterone receptor A (PRA)/progesterone receptor B (PRB) in ovarian cancer patients which might be the rationale for putative new treatment strategies. Patients and methods: The presence of NRF2 and PRA/PRB was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC). Staining of NRF2 and PRA/ PRB was rated using the semi-quantitative immunoreactive score (IR score, Remmele's score) and correlated to clinical and pathological data. NRF2 and PRA/PRB expression were compared with respect to the overall survival (OS). Results: NRF2 staining was different in both, the cytoplasm and nucleus between the histological subtypes (p=0.001 and p=0.02, respectively). There was a significant difference in the PRA expression comparing all histological subtypes (p=0.02). Histological subtypes showed no significant differences in the PRB expression. A strong correlation of cytoplasmic NRF2 and PRA expression was detected (cc=0.247, p=0.003) as well as of cytoplasmic NRF2 and PRB expression (cc=0.25, p=0.003), confirmed by immunofluorescence double staining. Cytoplasmic NRF2 expression was associated with a longer OS (median 50.6 vs 32.5 months; p=0.1) as it was seen for PRA expression (median 63.4 vs 33.1 months; p=0.08), although not statistically significant. In addition, high PRB expression (median 80.4 vs 32.5 months; p=0.04) and concurrent expression of cytoplasmic NRF2 and PRA were associated with a significantly longer OS (median 109.7 vs 30.6 months; p=0.02). The same relationship was also noted for NRF2 and PRB with improved OS for patients expressing both cytoplasmic NRF2 and PRB (median 153.5 vs 30.6 months; p=0.009). Silencing of NFE2L2 induced higher mRNA expression of PGR in the cancer cell line OVCAR3 (p>0.05) confirming genetic interactions of NRF2 and PR. Conclusion: In this study, the combination of cytoplasmic NRF2 and high PRA/PRB expression was demonstrated to be associated with improved overall survival in ovarian cancer patients. Further understanding of interactions within the NRF2/AKR1C1/PR pathway could open new additional therapeutic approaches.