G Emons

Georg-August-Universität Göttingen, Göttingen, Lower Saxony, Germany

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Publications (350)698.93 Total impact

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    ABSTRACT: Due to the lack of ERalpha, triple negative breast cancers (TNBCs) are not susceptible to endocrine therapy using antiestrogens. However, the majority of TNBCs express the membrane bound estrogen receptor GPR30. We have recently shown that knock-down of GPR30 expression prevented growth stimulation of TNBC cell lines by 17beta-estradiol. Now we analyzed whether specific inhibition of GPR30 represents a new option for therapy of TNBC. Growth of TNBC cells was assessed using Alamar-blue colorimetric assay. Activation of c-Src and EGF-receptor was assessed using Western blots. Expression of c-fos, cyclin D1 and aromatase was quantified by RT-PCR. Galpha-specific signaling of GPR30 was analyzed by electrophoretic mobility shift assay. HCC1806 cells showed the highest GPR30 expression, in HCC70 cells it was clearly lower, in MDA-MB-231 cells it was lowest. 10-8 M 17beta-estradiol significantly increased proliferation of HCC1806 cells to 134 +/- 12% of control (p < 0.01). Proliferation of HCC70 cells was slightly increased to 116 +/- 8% of control. Estriol significantly reduced cell number of HCC1806 cells to 16 +/- 12% (p < 0.01). Cell number of HCC70 cells and of MDA-MB-231 cells was reduced to 68 +/- 25% and to 61 +/- 10%, respectively.Activity of Src kinase increased to 150 +/- 10% (p < 0.05) by 10-8 M 17beta-estradiol treatment in HCC1806 and to 220 +/- 20% in HCC70 cells (p < 0.01). Estriol treatment completely inhibited 17beta-estradiol-induced p-src activation. Transactivation of EGF-receptor increased by estradiol treatment to 350% in HCC1806 and to 280% in HCC70 cells. Estriol completely suppressed EGF-receptor transactivation. c-fos expression increased to 260% and to 190%, respectively. Estriol reduced this induction to 160% (HCC1806) and below control in HCC70 cells. Cyclin D1 was induced to 290% (HCC1806) and 170% (HCC70) and completely inhibited by estriol. 17beta-estradiol increased CREB-phosphorylation to 400%. Binding of phospho-CREB to a CRE of cyclin D1 was enhanced to 320%. Specific pharmacological inhibition of GPR30 might become a promising targeted therapy for TNBC in future.
    BMC Cancer 12/2014; 14(1):935. · 3.32 Impact Factor
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    ABSTRACT: Metastasis to bone is a frequent problem of advanced breast cancer. Particularly breast cancers, which do not express estrogen receptor α (ERα) and progesterone receptor (PR) and which have no overexpression of human epidermal growth factor receptor 2 (HER2), so‑called triple‑negative breast cancers (TNBCs), are considered as very aggressive and have a poor prognosis. Recently we have shown that breast cancer cell invasion was dramatically increased when co‑cultured with MG63 osteoblast‑like cells. Using this model we have now analyzed whether estrogen receptor β (ERβ) plays a role in TNBC cell invasion in vitro. ERα and ERβ protein expression was analyzed using western blot analysis. Invasion was quantified by assessment of TNBC cell migration rate through an artificial basement membrane in a modified Boyden chamber during co‑culture with MG63 osteoblast‑like cells. The effects of ERβ agonist treatment on CXC motif chemokine receptor 4 (CXCR4) protein expression during co‑culture with MG64 cells was quantified using western blot analysis. Proliferation was measured using alamarBlue assay. TNBC cell lines HCC1806 and HCC1937 showed no ERα but high ERβ protein expression. Cell invasion of HCC1806 and HCC1937 TNBC cells was significantly increased when co‑cultured with MG63 osteoblast‑like cells. Treatment with ERβ selective estrogen agonists liquiritigenin and ERB‑041 reduced the ability to invade a reconstituted basement membrane and to migrate in response to the cellular stimulus. During co‑culture CXCR4 protein expression of TNBC cell lines HCC1806 and HCC1937 was significantly increased. Treatment with liquiritigenin resulted in a significant decrease of CXCR4 protein expression. Both ERβ agonists showed no effect on TNBC cell proliferation. Our findings suggest that ERβ plays a major role in TNBC invasion. Bone‑directed invasion can be inhibited by ERβ agonists.
    International journal of oncology. 11/2014;
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    ABSTRACT: Epithelial-mesenchymal transition (EMT) is a cellular development program characterized by loss of cell adhesion and increased cell mobility. It is essential for numerous processes including metastasis. In this study we have generated "aggressive" MCF-7 breast cancer cells (MCF-7-EMT), which show significantly increased invasion in contrast to wild type MCF-7 (MCF-7 WT) cells. In addition, we have analyzed, whether these cell lines differ in their metastatic behavior in vivo and in expression of invasion and/or EMT-relevant genes. Invasive behavior of different human breast cancer cell lines was tested. "Aggressive" MCF-7 cells (MCF-7-EMT) were generated using coculture and mammosphere culture techniques. To analyze whether or not MCF-7-EMT cells in contrast to MCF-7 WT cells form metastases in vivo, we assessed metastases in a nude mouse model. mRNA expression profiles of MCF-7 WT cells and MCF-7-EMT cells were compared using the Affymetrix micro array technique. Expression of selected genes was validated using real-time PCR. In addition, protein expression of epithelial marker E-cadherin (CDH1) and mesenchymal markers N-cadherin (CDH2), Vimentin (VIM), and TWIST was compared. The breast cancer cell lines showed different invasive behavior from hardly any invasion to a stronger cell movement. Coculture with osteoblast-like MG63 cells led to significantly increased cell invasion rates. The highest increase was shown using MCF-7 WT cells. Generated MCF-7-EMT cells showed significantly increased invasion as compared to MCF-7 WT cells. In 8 of 10 mice bearing orthotopically growing MCF-7-EMT tumors, we could detect metastases in liver and lung. In mice bearing MCF-7 WT tumors (n = 10), no metastases were found. MCF-7 WT cells and MCF-7-EMT cells were different in expression of 325 genes. Forty-four of the most regulated 50 invasion and/or EMT-related genes were upregulated and 6 genes were downregulated in MCF-7-EMT cells. Protein expression of mesenchymal markers CDH2, VIM, and TWIST was clearly increased in MCF-7-EMT cells. Protein expression of epithelial marker CDH1 was clearly decreased. With the breast cancer cell lines, MCF-7-EMT and MCF-7 WT cells, we have an excellent model of cells for further studies of EMT and invasion in vitro and in vivo.
    Breast Cancer Research and Treatment 10/2014; · 4.47 Impact Factor
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    ABSTRACT: Die Puerperalsepsis, hervorgerufen durch Streptokokken der Gruppe A, ist heutzutage eine seltene, jedoch bei Auftreten immer noch schwere und potentiell tödliche Erkrankung. Schweres Krankheitsgefühl postpartal sollte dringend ernst genommen werden, eine frühzeitige Antibiotikatherapie vor Manifestation der Sepsis ist lebensrettend. Fragestellung Sechzehn Stunden nach unauffälliger primärer Sectio wegen Abfalls der fetalen Herzfrequenz in der Schwangerschaftswoche 28+1 nach abgeschlossener Lungenreifeinduktion trat bei einer indischen 42-Jährigen III-Gravida/ III-Para ein akuter Schockzustand mit ausgeprägtem systemic inflammatory response Syndrom auf. Erst wenige Tage zuvor war die Schwangerschaft diagnostiziert und umgehend die stationäre Aufnahme bei arterieller Hypertonie und Verdacht auf Plazentainsuffizienz indiziert worden. ERGEBNIS In den Abstrichen fanden sich Streptococcus pyogenes und histopathologisch am Uterus eine suffiziente Narbe ohne Entzündungsnachweis sowie ein unauffälliges Myom. Es ist von einer aufsteigenden Infektion durch Streptococcus pyogenes auszugehen; pathologisch gesichert wurde lediglich eine floride, fibrinöse Peritoneitis mit umgebender Fettgewebsnekrose. Bei den erforderlichen Folgeoperationen wurde zudem eine nekrotisierende Fasziitis diagnostiziert. Der bei der Geburt 980g schwere Frühgeborene, APGAR 1/6/8, pH 7,35, konnte nach 15 Wochen Betreuung gesund entlassen werden. Die Entlassung seiner Mutter erfolgte weitere vier Wochen später in einem stabilen Zustand und ohne Anhalt für Residuen.
    60. Jahrestagung DGGG, München; 09/2014
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    ABSTRACT: Fallbericht: Foudroyante Puerperalsepsis durch hämolysierende Streptokokken Gruppe A mit toxic shock Syndrom Fragestellung: Sechzehn Stunden nach unauffälliger primärer Sectio wegen Abfalls der fetalen Herzfrequenz in der SSW 28+1 nach abgeschlossener Lungenreifeinduktion trat ein akuter Schockzustand mit ausgeprägtem systemic inflamatory response Syndrom auf. Verlauf: Bei Abfall der Sauerstoffsättigung und Tachykardie wurde zunächst zum Ausschluss einer Lungenembolie eine Thorax-CT durchgeführt. Sonographisch zeigte sich zunehmend freie Flüssigkeit im Abdomen, so dass relaparotomiert wurde: Bei zwei Litern putrider Flüssigkeit intraabdominell erfolgte eine Hysterektomie, Spülung, Eröffnung des Retroperitonealraums und Revision der Ovarica-Gefäße. Postoperativ zeigten sich eine schwerste Oxygenierungsstörung, ein akutes Nieren- und Gerinnungsversagen, eine Lebersynthesestörung, eine schlechte Hämodynamik und eine NO-vermittelte Relaxation der glatten Gefäßmuskulatur. Es entwickelten sich unter anderem septische pulmonale Streuherde, eine Beckenvenenthrombose der Vena iliaca externa, eine nekrotisierende Fasziitis der Bauchdecken sowie eine critical illness polyneuropathy und Polymyopathie. Ergebnis: In den Abstrichen fanden sich Streptococcus pyogenes und histopathologisch am Uterus eine suffiziente Narbe ohne Entzündungsnachweis sowie ein unauffälliges Myom. Es ist von einer aufsteigenden Infektion durch Streptokokkus pyogenes auszugehen; pathologisch gesichert wurde lediglich eine floride, fibrinöse Peritonitis mit umgebenden Fettgewebsnekrosen. Bei den erforderlichen Folgeoperationen wurde zudem eine nekrotisierende Fasziitis diagnostiziert. Der bei Geburt 980 g schwere Frühgeborene, APGAR 1/6/8, pH 7,35, konnte nach fünfzehn Wochen Betreuung gesund entlassen werden. Die Entlassung seiner Mutter erfolgte weitere vier Wochen später in einem stabilem Zustand und ohne Residuen. Schlussfolgerung: Die Puerperalsepsis, hervorgerufen durch Streptokokken der Gruppe A, ist heutzutage ein seltenes, jedoch bei Auftreten schweres und potentiell tödliches Krankheitsbild. Schweres Krankheitsgefühl postpartal sollte dringend ernst genommen werden, eine frühzeitige Antibiotikatherapie vor Manifestation der Sepsis ist lebensrettend.
    Geburtshilfe und Frauenheilkunde 09/2014; · 0.85 Impact Factor
  • Geburtshilfe und Frauenheilkunde 08/2014; 74(8):764-767. · 0.85 Impact Factor
  • Senologie - Zeitschrift für Mammadiagnostik und -therapie 05/2014; 11(02).
  • G. Emons, P. Mallmann
    Geburtshilfe und Frauenheilkunde 04/2014; 74(03):244-247. · 0.96 Impact Factor
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    ABSTRACT: To evaluate the activity and toxicity of AEZS-108 (Zoptarelin Doxorubicin Acetate) an LHRH agonist linked to doxorubicin in women with platinum refractory or resistant ovarian cancer expressing LHRH receptors. Women with epithelial ovarian, fallopian tube or primary peritoneal cancer, expressing LHRH receptors were eligible for this trial, when they had progression during treatment with a platinum based regimen or within 6months after receiving a platinum based regimen and a previous taxane treatment. At least one measurable target lesion (RECIST) or CA-125 levels higher than twice the upper limit of normal range (GCIG-criteria) were required. Patients received AEZS-108 (267mg/m(2) equimolar to 76.8mg/m(2) of free doxorubicin) every 3weeks as a two hour i.v. infusion. Fifty-five of 59 (93%) of ovarian cancer samples screened expressed LHRH receptors. 42 patients were enrolled in this study and received at least 1 infusion of AEZS-108 (ITT population). Of these 42 patients 6 (14.3%) had a partial response, 16 (38%) stable disease, 16 (38%) progressive disease and 4 patients were not evaluable. Median time to progression was 12weeks (95% CI: 8 - 20weeks), median overall survival was 53weeks (95% CI: 39 - 73weeks). Toxicity profile was favourable. AEZS-108 has a clinical activity in platinum refractory/resistant ovarian cancer which seems to be comparable to that of pegylated liposomal doxorubicin or to topotecan. Toxicity was comparably low. These data support the concept of a targeted chemotherapy for tumors expressing LHRH receptors.
    Gynecologic Oncology 04/2014; · 3.69 Impact Factor
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    ABSTRACT: Advanced or recurrent endometrial cancer (EC) no longer amenable to surgery or radiotherapy is a life-threatening disease with limited therapeutic options left. Eighty percent of ECs express receptors for luteinizing hormone-releasing hormone (LHRH), which can be targeted by AEZS-108 (zoptarelin doxorubicin acetate). This phase 2 trial was performed to assess the efficacy and safety of AEZS-108 in this group of patients. Patients had FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) III or IV or recurrent EC, LHRH receptor-positive tumor status, and at least had 1 measurable lesion (Response Evaluation Criteria in Solid Tumors). Prior anthracycline therapy was not allowed. Patients received AEZS-108 as a 2-hour infusion on day 1 of a 21-day cycle. The treatment was continued for a maximum of 6 to 8 cycles. The primary end point was the response rate determined by the Response Evaluation Criteria in Solid Tumors. From April 2008 to November 2009, 44 patients were included in the study at 8 centers in Germany (AGO) and 3 centers in Bulgaria. Forty-three of these patients were eligible. Two (5%) patients had a complete remission, and 8 (18%) achieved a partial remission. Stable disease for at least 6 weeks was observed in 44%. The median time to progression was 7 months, and the median overall survival was 15 months. The most frequently reported grade 3 or 4 adverse effects were neutropenia (12%) and leucopenia (9%). AEZS-108, an LHRH-agonist coupled to doxorubicin, has significant activity and low toxicity in women with advanced or recurrent LHRH receptor-positive EC, supporting the principle of receptor-mediated targeted chemotherapy.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
    International Journal of Gynecological Cancer 01/2014; · 1.94 Impact Factor
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    ABSTRACT: The cross talk between metastatic cancer cells and target sites is critical for the development and progression of metastases. Disruption of this interaction will allow to design mechanism-based effective and specific therapeutic interventions for metastases. We have established a coculture system of cells derived from different tumor entities and MG63 human osteoblastlike cells to analyze tumor cell invasion. Recently, we have shown that breast cancer cell invasion was dramatically increased when cocultured with MG63 cells.Using this model, we have now analyzed whether stromal-derived factor 1 (SDF-1) is responsible for human endometrial cancer cell invasion and whether kisspeptin-10 (KP-10) treatment affects SDF-1-induced invasion of endometrial cancer cells in vitro. Invasion was quantified by assessment of endometrial cancer cell migration rate through an artificial basement membrane in a modified Boyden chamber during coculture with MG63 cells or after treatment with SDF-1α, SDF-1β, or the combination of both SDF-1 isoforms. In addition, the role of SDF-1 in invasion of endometrial cancer cells was analyzed by blocking SDF-1 secretion during coculture with MG64 cells. Furthermore, the effects of KP-10 treatment on MG63 coculture-driven and SDF-1-induced invasion were analyzed. Endometrial cancer cell invasion was significantly increased when cocultured with MG63 cells. Treatment with KP-10 reduced the ability to invade a reconstituted basement membrane and to migrate in response to the cellular stimulus. This effect was significant in a dose window of 10 to 10 mol/L. During coculture, SDF-1 protein expression of MG63 cells was significantly increased. The MG63 coculture-induced increase of endometrial cancer cell invasion could be blocked by anti-SDF-1 antibodies. Treatment of endometrial cancer cells in monoculture (without MG63) with SDF-1α, SDF-1β, or the combination of both isoforms resulted in a significant increase of endometrial cancer cell invasion. The SDF-1-induced increase of endometrial cancer cell invasion was significantly reduced after treatment with KP-10. Our findings suggest that SDF-1 plays a major role in endometrial cancer invasion. Stromal-derived factor 1-induced invasion can be inhibited by KP-10 treatment.
    International Journal of Gynecological Cancer 01/2014; · 1.94 Impact Factor
  • Geburtshilfe und Frauenheilkunde 10/2013; 73(09):871-871. · 0.96 Impact Factor
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    ABSTRACT: The S2k guideline "Diagnostics and Therapy for Cervical Cancer" published in 2008 is currently being revised to the S3 level. Current developments in epidemiology, surgical therapy, radiochemotherapy and drug therapy will be presented. The S2k guideline "Diagnostics and Therapy for Endometrial Cancer" will also be up-dated this year. The revised recommendations on early diagnosis and diagnostics, therapy for precursors, surgical therapy, adjuvant therapy and therapy for recurrences and metastases will be presented.
    Geburtshilfe und Frauenheilkunde 09/2013; 73(9):908-910. · 0.96 Impact Factor
  • Geburtshilfe und Frauenheilkunde 09/2013; 73(9):874-889. · 0.96 Impact Factor
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    ABSTRACT: OBJECTIVES: To evaluate the activity and toxicity of fulvestrant, a pure estrogen receptor antagonist in patients with advanced or recurrent endometrial cancer, expressing estrogen and/or progesterone receptors (ER/PR). METHODS: Eligible patients with advanced or recurrent endometrial cancer not amenable to curative surgery and/or radiotherapy were treated with fulvestrant at a dose of 250mg by IM injection every 4weeks for at least 12weeks. Therapy was continued until disease progression, death, intolerable side effects or end of study. Response was assessed in patients with at least one target lesion according to WHO-criteria. RESULTS: Thirty-five patients were enrolled in this study and received at least one injection of fulvestrant (intention to treat-population, ITT). Twenty six patients received the intended 3 injections of fulvestrant (per protocol population, PP). There was no complete response but 4 partial responses (11.4% ITT) and 8 stable diseases. The median time to progression was 2.3months (ITT). Overall survival was 13.2months (ITT). Treatment was well tolerated. CONCLUSIONS: Fulvestrant at a dose of 250mg IM every 4weeks has marginal activity and good tolerability in patients with ER and/or PR positive advanced or recurrent endometrial cancer. A loading dose strategy and the use of 500mg/4weeks might improve the efficacy of this treatment.
    Gynecologic Oncology 03/2013; · 3.69 Impact Factor
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    ABSTRACT: The value of transvaginal ultrasound in gynaecological examinations is beyond dispute. But it is of particular forensic importance that the validity of this type of imaging with regard to the reliable detection of early-stage malignancy is properly understood. Vaginal ultrasound screening in asymptomatic patients for the early detection of endometrial carcinoma is not useful from a medical point of view, nor is it cost-efficient. However, even though the validity of transvaginal ultrasound for screening has currently not been proven, the method should still be an integral part of gynaecological examinations.
    Geburtshilfe und Frauenheilkunde 12/2012; 72(12):1088-1091. · 0.85 Impact Factor
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    ABSTRACT: Kisspeptins are peptides derived from the metastasis suppressor gene KISS1 interacting with GPR54 as their corresponding receptor. The KISS1/GPR54 system is one regulator of cellular motility mechanisms leading to decreased migration and invasion. Its role in cell proliferation processes is not clearly understood. In this study, breast cancer cell lines, T47D, ZR75-1, MDA‑MB‑231, MDA‑MB‑435s, MDA‑MB‑453, HCC 70, HCC 1806, HCC 1937 and MCF‑7, were investigated for their endogenous GPR54 expression by immunocytochemistry, RT‑PCR and western blot analysis. The effect of kisspeptin‑10 on proliferation was measured in MDA‑MB‑231, MDA‑MB‑435s, HCC 1806 and MCF‑7 cells. Further experiments on proliferation were carried out with cells transfected with GPR54. All of the tested breast cancer cell lines expressed GPR54 in different amounts. No effects on proliferation were detected in the breast cancer cells expressing the receptor endogenously. In transfected neuronal cells overexpressing GPR54, proliferation was significantly inhibited by kisspeptin‑10. The results indicate that the antiproliferative action of kisspeptin depends on the nature of GPR54 expression. The effect was detected in an artificial system of cells transfected with GPR54 and not in cells expressing the receptor endogenously. Thus, the antiproliferative action of kisspeptin seems not to be important for pathophysiological processes.
    Oncology Reports 11/2012; · 2.19 Impact Factor
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    ABSTRACT: OBJECTIVE: Increased glycolysis for energy production is necessary for survival of tumor cells and thus represents a selective therapeutic target. We have analyzed in vitro whether inhibition of glycolysis can reduce the viability of human endometrial and ovarian cancer cells and whether it can enhance the antitumor efficacy of GnRH receptor-targeted therapies. MATERIALS AND METHODS: Cell viability of ovarian and endometrial cancer cells treated without or with glycolysis inhibitor 2-Deoxy-D-Glucose (2DG) alone or in combination with GnRH-II antagonist [Ac-D2Nal, D-4Cpa, D-3Pal,Leu, D-Ala]GnRH-II or with cytotoxic GnRH-I agonist AEZS-108 (AN-152) was measured using alamar blue assay. Induction of apoptosis was analyzed using TUNEL assay and quantified by measurement of loss of mitochondrial membrane potential. Apoptotic signaling was measured by quantification of activated caspase-3 by using the Western blot technique. RESULTS: Treatment of endometrial and ovarian cancer cells with glycolysis inhibitor 2DG resulted in a significant decrease of cell viability and a significant increase of apoptosis. Treatment with 2DG in combination with the GnRH-II antagonist or with AEZS-108 resulted in a significant reduced viability compared with single-agent treatments. The observed reduction in viability was due to induction of apoptosis. Also for apoptosis induction, a significant stronger effect in the case of cotreatments compared with single-agent treatments could be observed. These additive effects could be correlated to increased activation of caspase-3. CONCLUSIONS: The glycolytic phenotype of human endometrial and ovarian cancer cells can be targeted for therapeutic intervention. In addition, cotreatment of a glycolysis inhibitor with GnRH receptor-targeted therapies might be a suitable therapy for GnRH receptor-positive human endometrial and ovarian cancers.
    International Journal of Gynecological Cancer 11/2012; · 1.94 Impact Factor
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    ABSTRACT: OBJECTIVE: To analyze in a large prospective cohort study of low risk pregnancies whether cell-free fetal (cff) DNA in maternal plasma of the second trimester might be associated with the development of preeclampsia, preterm delivery, and small for gestational age. STUDY DESIGN: A subset of a large prospective cohort study in serological RhD negative pregnant women with RHD positive fetuses was used. Cff DNA was determined through the detection of RHD specific sequences with real-time PCR. RESULTS: In 611 pregnancies, rates of 7.2% preeclampsia, 1.6% preterm birth ≤32, 2.9% ≤34, and 12.4% ≤37 weeks of gestation, 5.7% of small for gestational age <5th percentile, and 8.2% <10th percentile were observed. For none of these risk groups an association with cff DNA could be established. CONCLUSION: Cff DNA in maternal plasma of the second trimester was not found to be a marker for an adverse pregnancy outcome in low risk pregnancies.
    European journal of obstetrics, gynecology, and reproductive biology 09/2012; · 1.97 Impact Factor
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    ABSTRACT: Endocrine resistance in breast cancer remains a major clinical problem and is caused by crosstalk mechanisms of growth factor receptor cascades, such as the erbB and PI3K/AKT pathways. The possibilities a single breast cancer cell has to achieve resistance are manifold. We developed a model of 4-hydroxy-tamoxifen (OHT)‑resistant human breast cancer cell lines and compared their different expression patterns, activation of growth factor receptor pathways and compared cells by genomic hybridization (CGH). We also tested a panel of selective inhibitors of the erbB and AKT/mTOR pathways to overcome OHT resistance. OHT‑resistant MCF-7-TR and T47D-TR cells showed increased expression of HER2 and activation of AKT. T47D-TR cells showed EGFR expression and activated MAPK (ERK-1/2), whereas in resistant MCF-7-TR cells activated AKT was due to loss of CTMP expression. CGH analyses revealed remarkable aberrations in resistant sublines, which were predominantly depletions. Gefitinib inhibited erbB signalling and restored OHT sensitivity in T47D-TR cells. The AKT inhibitor perifosine restored OHT sensitivity in MCF-7-TR cells. All cell lines showed expression of receptors for gonadotropin-releasing hormone (GnRH) I and II, and analogs of GnRH-I/II restored OHT sensitivity in both resistant cell lines by inhibition of erbB and AKT signalling. In conclusion, mechanisms to escape endocrine treatment in breast cancer share similarities in expression profiling but are based on substantially different genetic aberrations. Evaluation of activated mediators of growth factor receptor cascades is helpful to predict response to specific inhibitors. Expression of GnRH-I/II receptors provides multi-targeting treatment strategies.
    International Journal of Oncology 08/2012; 41(5):1845-54. · 2.77 Impact Factor

Publication Stats

4k Citations
698.93 Total Impact Points

Institutions

  • 1998–2014
    • Georg-August-Universität Göttingen
      • Faculty of Medicine
      Göttingen, Lower Saxony, Germany
  • 2000–2012
    • Universitätsmedizin Göttingen
      • • Department of Gynecology and Obstetrics
      • • Center for Gynecology
      Göttingen, Lower Saxony, Germany
    • University of Hamburg
      Hamburg, Hamburg, Germany
  • 2004
    • Robert Koch Institut
      Berlín, Berlin, Germany
  • 2003
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
  • 1991–2003
    • Philipps-Universität Marburg
      • Klinik für Gynäkologie, Gynäkologische Endokrinologie und Onkologie (Marburg)
      Marburg an der Lahn, Hesse, Germany
  • 1985–1999
    • Universität zu Lübeck
      • • Department of Obstetrics and Gynecology
      • • Klinik für Frauenheilkunde und Geburtshilfe
      Lübeck, Schleswig-Holstein, Germany
  • 1996
    • Tulane University
      New Orleans, Louisiana, United States
  • 1990
    • West Georgia Obstetrics and Gynecology
      Georgetown, Georgia, United States
  • 1988
    • National Institute of Child Health and Human Development
      Maryland, United States