Author: "A G, Zeimet" - Searchworks@Jio Institute Digital Library Search Results

217 results on '"A G, Zeimet"'

1. BRCA loss of function including BRCA1 DNA-methylation, but not BRCA-unrelated homologous recombination deficiency, is associated with platinum hypersensitivity in high-grade ovarian cancer

Author: Heidelinde Fiegl, Simon Schnaiter, Daniel U. Reimer, Katharina Leitner, Petra Nardelli, Irina Tsibulak, Verena Wieser, Katharina Wimmer, Esther Schamschula, Christian Marth, and Alain G. Zeimet
Subjects: Ovarian cancer, BRCA1, BRCA2, DNA-methylation, Homologous recombination deficiency (HRD), Platinum sensitivity, Medicine, Genetics, QH426-470
Abstract: Abstract Background In high-grade ovarian cancer (HGOC), determination of homologous recombination deficiency (HRD) status is commonly used in routine practice to predict response to platinum-based therapy or poly (ADP-ribose) polymerase inhibitors (PARPi). Here we tested the hypothesis that BRCA loss of function (LOF) due to epigenetic or genetic aberrations is a better predictor for the clinical outcome than HRD. One hundred thirty-one HGOC tissues were tested for BRCA DNA-methylation, BRCA mutations, HRD and BRCA1 mRNA expression, followed by a comprehensive survival analysis. Results BRCA1-methylation was detected in 11% of the tumors, exclusively in BRCA1-wild-type (wt) HGOCs. BRCA1-methylated tumors (BRCA1-meth) had HRD-scores similar to those of BRCA-mutated (mut) tumors, and higher compared to unmethylated-BRCA-wt tumors (BRCA-wt-unmeth; P
Published: 2024
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2. The game-changing impact of POLE mutations in oncology—a review from a gynecologic oncology perspective

Author: Johanna Kögl, Teresa L. Pan, Christian Marth, and Alain G. Zeimet
Subjects: POLE mutations, EDM, ultramutation, tumor mutational burden, hotspot mutations, endometrial cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Somatic mutations within the exonuclease proofreading domain (EDM) of the DNA polymerase Pol ϵ (POLE) gene are increasingly being discovered in ovarian, colorectal, urological, and, especially, endometrial carcinoma (EC), where these are found in up to 10% of the cases. In EC, there are five confirmed pathogenic somatic POLE-EDM mutations that are located at codons 286, 411, 297, 456, and 459, and these are called “hotspot” mutations. POLE mutant tumors are ultramutated entities with a frequency of base substitution mutations that is among the highest in human tumors. Interestingly, these mutations are associated with excellent clinical outcome in EC. An additional six “non-hotspot” POLE-EDM EC mutations are also considered pathogenic, and they also confer a favorable prognosis. Currently, de-escalation of adjuvant treatment is recommended for patients with EC with stage I–II tumors involving any of these 11 EDM mutations, even in patients with other clinicopathological risk factors. The high tumor mutational burden and the consequent increased infiltration of immune cells due to the overexpression of different neoantigens are probably responsible for the improved prognosis. Ongoing studies are examining POLE hotspot mutations among many non-gynecologic tumors, although the impact of such mutations on clinical outcomes is still a topic of debate. Therapeutic modalities for these hypermutated tumors are also an important consideration, including the need for or de-escalation of adjuvant treatments and the response to immune therapy. This review addresses the critical role of POLE mutations in gynecologic oncology and oncology in general, focusing on definitions, variants, underlying pathogenic mechanisms, upcoming developments in the field, and the clinic behavior associated with such mutations.
Published: 2024
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3. PBRM1 mutations might render a subtype of biliary tract cancers sensitive to drugs targeting the DNA damage repair system

Author: Kai Zimmer, Florian Kocher, Gerold Untergasser, Brigitte Kircher, Arno Amann, Yasmine Baca, Joanne Xiu, W. Micheal Korn, Martin D. Berger, Heinz-Josef Lenz, Alberto Puccini, Elisa Fontana, Anthony F. Shields, John L. Marshall, Michael Hall, Wafik S. El-Deiry, David Hsiehchen, Teresa Macarulla, Josep Tabernero, Renate Pichler, Moh’d Khushman, Upender Manne, Emil Lou, Dominik Wolf, Viktorija Sokolova, Simon Schnaiter, Alain G. Zeimet, Pat Gulhati, Gerlig Widmann, and Andreas Seeber
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Polybromo-1 (PBRM1) loss of function mutations are present in a fraction of biliary tract cancers (BTCs). PBRM1, a subunit of the PBAF chromatin-remodeling complex, is involved in DNA damage repair. Herein, we aimed to decipher the molecular landscape of PBRM1 mutated (mut) BTCs and to define potential translational aspects. Totally, 1848 BTC samples were analyzed using next-generation DNA-sequencing and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). siRNA-mediated knockdown of PBRM1 was performed in the BTC cell line EGI1 to assess the therapeutic vulnerabilities of ATR and PARP inhibitors in vitro. PBRM1 mutations were identified in 8.1% (n = 150) of BTCs and were more prevalent in intrahepatic BTCs (9.9%) compared to gallbladder cancers (6.0%) or extrahepatic BTCs (4.5%). Higher rates of co-mutations in chromatin-remodeling genes (e.g., ARID1A 31% vs. 16%) and DNA damage repair genes (e.g., ATRX 4.4% vs. 0.3%) were detected in PBRM1-mutated (mut) vs. PBRM1-wildtype (wt) BTCs. No difference in real-world overall survival was observed between PBRM1-mut and PBRM1-wt patients (HR 1.043, 95% CI 0.821–1.325, p = 0.731). In vitro, experiments suggested that PARP ± ATR inhibitors induce synthetic lethality in the PBRM1 knockdown BTC model. Our findings served as the scientific rationale for PARP inhibition in a heavily pretreated PBRM1-mut BTC patient, which induced disease control. This study represents the largest and most extensive molecular profiling study of PBRM1-mut BTCs, which in vitro sensitizes to DNA damage repair inhibiting compounds. Our findings might serve as a rationale for future testing of PARP/ATR inhibitors in PBRM1-mut BTCs.
Published: 2023
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4. A comparison of four technologies for detecting p53 aggregates in ovarian cancer

Author: Nicole Heinzl, Katarzyna Koziel, Elisabeth Maritschnegg, Astrid Berger, Elisabeth Pechriggl, Heidi Fiegl, Alain G. Zeimet, Christian Marth, Robert Zeillinger, and Nicole Concin
Subjects: p53, protein aggregation, ovarian cancer, immunofluorescence staining, immunoprecipitation, ELISA, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: The tumor suppressor protein p53 is mutated in half of all cancers and has been described to form amyloid-like structures, commonly known from key proteins in neurodegenerative diseases. Still, the clinical relevance of p53 aggregates remains largely unknown, which may be due to the lack of sensitive and specific detection methods. The aim of the present study was to compare the suitability of four different methodologies to specifically detect p53 aggregates: co-immunofluorescence (co-IF), proximity ligation assay (PLA), co-immunoprecipitation (co-IP), and the p53-Seprion-ELISA in cancer cell lines and epithelial ovarian cancer tissue samples. In 7 out of 10 (70%) cell lines, all applied techniques showed concordance. For the analysis of the tissue samples co-IF, co-IP, and p53-Seprion-ELISA were compared, resulting in 100% concordance in 23 out of 30 (76.7%) tissue samples. However, Co-IF lacked specificity as there were samples, which did not show p53 staining but abundant staining of amyloid proteins, highlighting that this method demonstrates that proteins share the same subcellular space, but does not specifically detect p53 aggregates. Overall, the PLA and the p53-Seprion-ELISA are the only two methods that allow the quantitative measurement of p53 aggregates. On the one hand, the PLA represents the ideal method for p53 aggregate detection in FFPE tissue, which is the gold-standard preservation method of clinical samples. On the other hand, when fresh-frozen tissue is available the p53-Seprion-ELISA should be preferred because of the shorter turnaround time and the possibility for high-throughput analysis. These methods may add to the understanding of amyloid-like p53 in cancer and could help stratify patients in future clinical trials targeting p53 aggregation.
Published: 2022
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5. Clinical impact of EZH2 and its antagonist SMARCA4 in ovarian cancer

Author: Katharina Leitner, Irina Tsibulak, Verena Wieser, Katharina Knoll, Daniel Reimer, Christian Marth, Heidi Fiegl, and Alain G. Zeimet
Subjects: Medicine, Science
Abstract: Abstract SMARCA4 and EZH2 are two functional key players of their respective antagonizing chromatin remodeling complexes SWI/SNF and PRC2. EZH2 inhibitory drugs may abrogate pro-oncogenic features of PRC2 and turn the balance to cell differentiation via SWI/SNF activity in cancers. SMARCA4 and EZH2 expression was assessed by RT-PCR in 238 epithelial ovarian cancers (OCs) and put in relation to clinico-pathological parameters and patients’ outcome. Optimal thresholds for high and low expression of both variables were calculated by the Youden’s index based on receiver operating characteristic (ROC) curves. High SMARCA4 mRNA expression was independently associated with favorable progression-free survival (PFS) (P = 0.03) and overall survival (OS) (P = 0.018). As Youden’s threshold determination for EZH2 yielded a S-shaped ROC-curve, two cut-off points (29th and 94th percentile) predicting opposite features were defined. Whereas EZH2 mRNA levels beyond the 29th percentile independently predicted poor PFS (P = 0.034), Cox-regression in EZH2 transcripts above the 94th percentile revealed a conversion from unfavorable to favorable PFS and OS (P = 0.009 and P = 0.032, respectively). High SMARCA4 expression associates with improved survival, whereas moderate/high EZH2 expression predicts poor outcome, which converts to favorable survival in ultra-high expressing OCs. This small OC subgroup could be characterized by REV7-abrogated platinum hypersensitivity but concomitant PARP-inhibitor resistance.
Published: 2020
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6. Correction to: Epigenetic regulation of L1CAM in endometrial carcinoma: comparison to cancer–testis (CT-X) antigens

Author: Uwe Schirmer, Heidi Fiegl, Marco Pfeifer, Alain G. Zeimet, Elisabeth Müller-Holzner, Peter K. Bode, Verena Tischler, and Peter Altevogt
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Following publication of the original article [1], we have been alerted to errors in Figs. 2 and 8. In Fig. 2B, the GAPDH loading control for Hec1A cells is shown twice in error (in Fig. 2B and Fig. 2C). In Fig. 8, in testis case 1 (first column) the MAGE-A4 staining panel was repeated and also appears as the NY-ESO-1 staining panel in error. The corrected versions of Fig. 2 and Fig. 8 are shown below. We apologize for this inconvenience.
Published: 2018
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7. Adjuvante Therapie des Endometriumkarzinoms

Author: P. Mallmann, D. Vordermark, P. Feyer, V. Hagen, S. Höcht, P. Niehoff, E. Petru, A.-G. Zeimet, O. Micke, and M. J. Battista
Published: 2022
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8. CDK12/13 inhibition in ovarian cancer cell lines

Author: H Fiegl, L Hovdar, F Handle, F Santer, I Tsibulak, V Wieser, M J Ausserlechner, S Schnaiter, A G Zeimet, and C Marth
Published: 2023
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9. Data from E2F3a Is Critically Involved in Epidermal Growth Factor Receptor–Directed Proliferation in Ovarian Cancer

Author: Alain G. Zeimet, Peter Altevogt, Karl Illmensee, Christian Marth, Elisabeth Müller-Holzner, Heidi Fiegl, Nicole Concin, Martin Erdel, Sergej Skvortsov, Svenja Riedle, Michael Hubalek, and Daniel Reimer
Abstract: We describe for the first time a new integral molecular pathway, linking transcription factor E2F3a to epidermal growth factor receptor (EGFR) activation in ovarian cancer cells. Investigations on the role of E2F family members in EGFR-mediated mitogenic signaling revealed that E2F3a was selectively upregulated following EGFR activation, whereas all other E2F family members remained unaffected. In contrast, EGF treatment of healthy ovarian surface epithelial and mesothelial cells yielded a selective upregulation of proliferation-promoting E2F1 and E2F2 without influencing E2F3a expression. In ovarian cancer cell lines, the extent of EGF-induced proliferative stimulus was closely related to the magnitude of E2F3a increase, and proliferation inhibition by E2F3a knockdown was not overcome by EGF exposure. Furthermore, the EGFR-E2F3a axis was found to be signal transducer and activator of transcription 1/3 dependent and the ratio of IFN-regulatory factor (IRF)-1 to IRF-2 was shown to be determinative for E2F3a control. In a pilot study on 32 primary ovarian cancer specimens, a highly significant correlation between activated EGFR and E2F3a expression was disclosed. This new integral pathway in the EGFR-driven mitogenic cell response, which through its key player E2F3a was found to be essential in triggering proliferation in ovarian cancer cells, provides new insights into EGFR signaling and could represent the basis for appealing new therapeutic approaches in ovarian cancer. Cancer Res; 70(11); 4613–23. ©2010 AACR.
Published: 2023
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10. Supplementary Figure 1 from DNA Hypomethylation and Ovarian Cancer Biology

Author: Melanie Ehrlich, Peter W. Laird, Alain G. Zeimet, Elisabeth Müller-Holzner, Christian Marth, Georg Goebel, Heidi Fiegl, Hannes M. Müller, Christian Woods, Guanchao Jiang, and Martin Widschwendter
Abstract: Supplementary Figure 1 from DNA Hypomethylation and Ovarian Cancer Biology
Published: 2023
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11. Supplementary Figure 2 from E2F3a Is Critically Involved in Epidermal Growth Factor Receptor–Directed Proliferation in Ovarian Cancer

Author: Alain G. Zeimet, Peter Altevogt, Karl Illmensee, Christian Marth, Elisabeth Müller-Holzner, Heidi Fiegl, Nicole Concin, Martin Erdel, Sergej Skvortsov, Svenja Riedle, Michael Hubalek, and Daniel Reimer
Abstract: Supplementary Figure 2 from E2F3a Is Critically Involved in Epidermal Growth Factor Receptor–Directed Proliferation in Ovarian Cancer
Published: 2023
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12. Supplementary Table 1 from DNA Hypomethylation and Ovarian Cancer Biology

Author: Melanie Ehrlich, Peter W. Laird, Alain G. Zeimet, Elisabeth Müller-Holzner, Christian Marth, Georg Goebel, Heidi Fiegl, Hannes M. Müller, Christian Woods, Guanchao Jiang, and Martin Widschwendter
Abstract: Supplementary Table 1 from DNA Hypomethylation and Ovarian Cancer Biology
Published: 2023
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13. Data from DNA Hypomethylation and Ovarian Cancer Biology

Author: Melanie Ehrlich, Peter W. Laird, Alain G. Zeimet, Elisabeth Müller-Holzner, Christian Marth, Georg Goebel, Heidi Fiegl, Hannes M. Müller, Christian Woods, Guanchao Jiang, and Martin Widschwendter
Abstract: Hypomethylation of some portions of the genome and hypermethylation of others are very frequent in human cancer. The hypomethylation often involves satellite 2 (Sat2) DNA in the juxtacentromeric (centromere-adjacent) region of chromosome 1. In this study, we analyzed methylation in centromeric and juxtacentromeric satellite DNA in 115 ovarian cancers, 26 non-neoplastic ovarian specimens, and various normal somatic tissue standards. We found that hypomethylation of both types of satellite DNA in ovarian samples increased significantly from non-neoplastic toward cancer tissue. Furthermore, strong hypomethylation was significantly more prevalent in tumors of advanced stage or high grade. Importantly, extensive hypomethylation of Sat2 DNA in chromosome 1 was a highly significant marker of poor prognosis (relative risk for relapse, 4.1, and death, 9.4) and more informative than tumor grade or stage. Also, comparing methylation of satellite DNA and 15 5′ gene regions, which are often hypermethylated in cancer or implicated in ovarian carcinogenesis, we generally found no positive or negative association between methylation changes in satellite DNA and in the gene regions. However, hypermethylation at two loci, CDH13 (at 16q24) and RNR1 (at 13p12), was correlated strongly with lower levels of Sat2 hypomethylation. The CDH13/Sat2 epigenetic correlation was seen also in breast cancers. We conclude that satellite DNA hypomethylation is an important issue in ovarian carcinogenesis as demonstrated by: (a) an increase from non-neoplastic tissue toward ovarian cancer; (b) an increase within the ovarian cancer group toward advanced grade and stage; and (c) the finding that strong hypomethylation was an independent marker of poor prognosis.
Published: 2023
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14. Supplementary Figure 3 from E2F3a Is Critically Involved in Epidermal Growth Factor Receptor–Directed Proliferation in Ovarian Cancer

Author: Alain G. Zeimet, Peter Altevogt, Karl Illmensee, Christian Marth, Elisabeth Müller-Holzner, Heidi Fiegl, Nicole Concin, Martin Erdel, Sergej Skvortsov, Svenja Riedle, Michael Hubalek, and Daniel Reimer
Abstract: Supplementary Figure 3 from E2F3a Is Critically Involved in Epidermal Growth Factor Receptor–Directed Proliferation in Ovarian Cancer
Published: 2023
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15. Supplementary Figure 1 from E2F3a Is Critically Involved in Epidermal Growth Factor Receptor–Directed Proliferation in Ovarian Cancer

Author: Alain G. Zeimet, Peter Altevogt, Karl Illmensee, Christian Marth, Elisabeth Müller-Holzner, Heidi Fiegl, Nicole Concin, Martin Erdel, Sergej Skvortsov, Svenja Riedle, Michael Hubalek, and Daniel Reimer
Abstract: Supplementary Figure 1 from E2F3a Is Critically Involved in Epidermal Growth Factor Receptor–Directed Proliferation in Ovarian Cancer
Published: 2023
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16. Treatment strategies in patients with gynecological sarcoma : Results of the prospective intergroup real-world registry for gynecological sarcoma in Germany (REGSA-NOGGO RU1)

Author: Eva Roser, Philipp Harter, Dario Zocholl, Dominik Denschlag, Radoslav Chekerov, Pauline Wimberger, Christian Kurzeder, Annette Hasenburg, Mustafa-Zelal Muallem, Alexander Mustea, Guenter Emons, A G Zeimet, Felix Beck, Tjadina Arndt, Sara Y Brucker, Stefan Kommoss, Florian Heitz, Julia Welz, Eva-Katharina Egger, Matthias Kalder, Paul Buderath, Maximilian Klar, Christian Marth, Uwe Andreas Ulrich, Michael Weigel, Lea Traub, Christoph Anthuber, Hans Strauss, Lars Hanker, Theresa Link, Karol Kubiak, Badrig Melekian, Daniela Hornung, Martin Pölcher, Bjoern Lampe, Thomas Krauß, Ulrich Keilholz, Anne Flörcken, Klaus Pietzner, and Jalid Sehouli
Subjects: Oncology, Medizin, Obstetrics and Gynecology
Abstract: ObjectiveGynecological sarcomas account for 3% of all gynecological malignancies and are associated with a poor prognosis. Due to the rarity and heterogeneity of gynecological sarcomas there is still no consensus on optimal therapeutic strategies. This study’s objective was to describe the treatment strategies used in patients with gynecological sarcomas in the primary course of disease.MethodsThe German prospective registry for gynecological sarcoma (REGSA) is the largest registry for gynecological sarcomas in Germany, Austria and Switzerland. Primary inclusion criteria for REGSA are histological diagnosis of sarcoma of the female genital tract, sarcoma of the breast or uterine smooth muscle tumors of uncertain malignant potential (STUMP). We evaluated data of the REGSA registry on therapeutic strategies used for primary treatment from August 2015 to February 2021.ResultsA total of 723 patients from 120 centers were included. Data on therapeutic strategies for primary treatment were available in 605 cases. Overall, 580 (95.9%) patients underwent primary surgery, 472 (81.4%) of whom underwent only hysterectomy. Morcellation was reported in 11.4% (n=54) of all hysterectomies. A total of 42.8% (n=202) had no further surgical interventions, whereas an additional salpingo-ophorectomy was performed in 54% (n=255) of patients. An additional lymphadenectomy was performed in 12.7% (n=60), an omentectomy in 9.5% (n=45) and intestinal resection in 6.1% (n=29) of all patients. Among 448 patients with available information, 21.4% (n=96) received chemo- or targeted therapies, more commonly as single-agent treatment than as drug combinations. Information about anti-hormonal treatment was available for 423 patients, among which 42 (9.9%) received anti-hormonal treatment, 23 (54.8%) of whom with low-grade endometrial stroma sarcomas. For radiotherapy, data of 437 patients were available, among which 29 (6.6%) patients underwent radiotherapy.ConclusionOur study showed that treatment of patients with gynecologic sarcomas is heterogeneous. Further trials are needed along with more information on treatment modalities, therapy response and patient-reported outcomes to implement new treatment strategies.
Published: 2023

17. Efficacy of an optimal ovarian cancer screening: a best-case scenario study based on real-world data

Author: Delmarko Irmgard, Tatjana Weiss, Michael Mossig, Walter Dirschlmayer, Alain G. Zeimet, Lena Steinkasserer, and Christian Marth
Subjects: Oncology, Survival rate, medicine.medical_specialty, endocrine system diseases, Disease, Carcinoma, Ovarian Epithelial, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Ovarian carcinoma, Cancer screening, Humans, Medicine, 030212 general & internal medicine, Stage (cooking), Early Detection of Cancer, Neoplasm Staging, Ovarian Neoplasms, business.industry, Stage-shift, Obstetrics and Gynecology, Cancer, General Medicine, Gynecologic Oncology, medicine.disease, female genital diseases and pregnancy complications, Austria, 030220 oncology & carcinogenesis, Female, medicine.symptom, business, Ovarian cancer, Cancer Screening
Abstract: Purpose To date, ovarian cancer screening in asymptomatic women has not shown a mortality benefit. The aim of this simulation study was to outline the impact of different histological subtypes on a potential stage-shift, achieved by screening. Methods Real-world data were derived in the period of 2000–2017 from the Klinischen Tumorregister Austria. We estimated five-year overall survival (OS) of patients with ovarian cancer regarding different histological subtypes and FIGO stages. A theoretical model was generated predicting the trend of OS mediated by an eventual down-shifting of ovarian cancer from FIGO stage III/IV to FIGO stage I/II by screening, considering the influence of different histological subtypes. Results 3458 ovarian cancer patients were subdivided according to histological subtypes and FIGO classification. Major difference in distribution of histological types was found between FIGO stage I/II and III/IV. A theoretical down-shift of tumors from high to low FIGO stages based on our registry calculations showed that the five-year OS would increase from 50% to nearly 80% by perfect screening. Conclusion In our simulation study, we showed that down-shifting ovarian cancers by successful screening might increase OS by 30 percentage point. Our results underscore the importance to recognize ovarian cancer as a heterogenous disease with distinct epidemiologic, molecular and clinical features. The individual characteristic of each histotype is of utmost impact on the definition of screening aims and may influence early detection and stage-shift. Efficacy of screening is mainly dependent on detection of high-risk cancer types and not the slow growing low-grade types.
Published: 2021
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18. Clinical impact of BRCA2 mRNA expression in high-grade serous ovarian cancer: validation using the TCGA cohort

Author: K Leitner, H Welponer, H Fiegl, Hubert Hackl, I Tsibulak, Verena Wieser, Alain G. Zeimet, and Christian Marth
Subjects: BRCA2 Protein, Ovarian Neoplasms, Oncology, medicine.medical_specialty, business.industry, Mrna expression, Hematology, General Medicine, 030218 nuclear medicine & medical imaging, Cohort Studies, Causes of cancer, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Cohort, Serous ovarian cancer, medicine, Humans, Female, Radiology, Nuclear Medicine and imaging, Epithelial ovarian cancer, RNA, Messenger, business
Abstract: Epithelial ovarian cancer (OC) is one of the leading causes of cancer death in women in the western world [1–3]. Approximately 10–15% of all epithelial OC are hereditary and the vast majority of th...
Published: 2020
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19. PARP inhibitors in the treatment of ovarian cancer

Author: Daniel Reimer, Verena Wieser, K Knoll, Alain G. Zeimet, and Christian Marth
Subjects: Oncology, Chemotherapy, medicine.medical_specialty, Bevacizumab, business.industry, medicine.medical_treatment, Poly ADP ribose polymerase, Therapeutic effect, Hematology, 030204 cardiovascular system & hematology, medicine.disease, Precision medicine, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Recurrent Ovarian Cancer, Internal medicine, medicine, 030212 general & internal medicine, Ovarian cancer, business, medicine.drug
Abstract: SummaryThe recent exciting findings on the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor (PARPi) maintenance therapy in the first-line and later lines of treatment in ovarian cancer are illustrated. Unprecedented advantages have been shown in first-line therapy not only in BRCA-mutated cancers, but also in tumor exhibiting a homologous recombination repair deficiency (HRD) unrelated to BRCA aberrations. The advantages of PARP maintenance therapy in around 50% of HR-proficient high-grade ovarian cancers are far less clear and, even though of statistical significance, the clinical benefit for the patients may be of borderline significance. The pre-treatment testing of HRD remains a matter of debate especially in the light of the current era of precision medicine. Data on the combination of PARPi with bevacizumab maintenance therapy uncovered additive beneficial therapeutic effects. In recurrent ovarian cancer, results on PARPi maintenance therapy after response to platinum-based reinduction chemotherapy are also excellent. At present, however, PARPi maintenance therapy remains reserved for PARPi-naive patients, since the data on PARPi after PARPi is extremely sparse.
Published: 2020
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20. JARID1B beim Ovarialkarzinom

Author: K Leitner, I Tsibulak, V Wieser, M Penz, H Fiegl, C Marth, and A G Zeimet
Published: 2022
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21. The miR-34 family and its clinical significance in ovarian cancer

Author: S Wenzel, H Welponer, Verena Wieser, Susanne Sprung, Hubert Hackl, H Fiegl, I Tsibulak, Alain G. Zeimet, Christian Marth, Giridhar Shivalingaiah, and C Degasper
Subjects: 0301 basic medicine, Oncology, p53, medicine.medical_specialty, medicine.disease_cause, survival, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Internal medicine, Medicine, Clinical significance, Progression-free survival, Inverse correlation, business.industry, miR-34, medicine.disease, Serous fluid, 030104 developmental biology, medicine.anatomical_structure, ovarian cancer, 030220 oncology & carcinogenesis, business, Carcinogenesis, Ovarian cancer, carcinogenesis, Fallopian tube, Research Paper
Abstract: The tumor suppressor miR-34 family is transcriptionally induced by p53. Clinical significance of the various miR-34 family members has not been studied in ovarian cancer. In 228 ovarian cancers and in 19 non-neoplastic fallopian tube samples we analysed miR-34 a/b/c expression in relation to clinicopathological characteristics and clinical outcome. We found significantly lower levels of miR-34 a/b/c in ovarian cancers as compared to control-tissues (P=0.002, P
Published: 2020

22. High RIG‐I expression in ovarian cancer associates with an immune‐escape signature and poor clinical outcome

Author: Verena Wieser, Heidi Fiegl, Alain G. Zeimet, Susanne Sprung, Dominik Wolf, Sieghart Sopper, Daniel Reimer, Christian Marth, Maximilian Boesch, and Gunther Hartmann
Subjects: Adult, Cancer Research, viruses, medicine.medical_treatment, chemical and pharmacologic phenomena, Tumor Immunology and Microenvironment, Kaplan-Meier Estimate, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Cancer immunotherapy, PD-L1, Biomarkers, Tumor, Tumor Microenvironment, medicine, Humans, Receptors, Immunologic, Aged, Neoplasm Staging, Proportional Hazards Models, Aged, 80 and over, Ovarian Neoplasms, Tumor microenvironment, biology, business.industry, virus diseases, FOXP3, Immunotherapy, Middle Aged, biochemical phenomena, metabolism, and nutrition, Prognosis, medicine.disease, Primary tumor, Oncology, Case-Control Studies, 030220 oncology & carcinogenesis, biology.protein, Cancer research, DEAD Box Protein 58, Biomarker (medicine), Female, Tumor Escape, Neoplasm Grading, biological phenomena, cell phenomena, and immunity, business, Ovarian cancer
Abstract: Ovarian cancer (OC) is the most lethal gynecological malignancy, with platinum‐based chemotherapy remaining the mainstay for adjuvant treatment after surgery. The lack of indication for immunotherapy may at least in part result from the lack of suitable biomarkers allowing stratification of potentially responding patients. In this monocentric study of 141 cases with OC, we used real‐time quantitative PCR to assess the expression of retinoic acid‐inducible gene‐I (RIG‐I) in primary tumor and healthy ovarian control tissues. RIG‐I expression was correlated to various clinicopathological characteristics as well as to a set of molecular and immunological markers. The prognostic significance of RIG‐I expression was queried in univariate and multivariate analyses and validated in an independent cohort. RIG‐I was overexpressed in the cancerous ovary and correlated with a higher tumor grade. The more aggressive Type‐II cancers and cancers with inactivating p53 mutations exhibited higher RIG‐I expression. RIG‐I levels were also elevated in cancers that recurred after remission or were platinum‐refractory. Survival analyses disclosed RIG‐I as an independent marker of poor outcome in OC. Continuative analyses revealed the molecular and immunological correlates of RIG‐I expression in the tumor microenvironment, including interferon production and a distinct immune‐regulatory signature involving checkpoint molecules (PD‐L1/PD‐1), the RNA‐editing enzyme ADAR1 and the regulatory T cell‐specific transcription factor FoxP3. We conclude that high RIG‐I expression associates with poor outcome in OC, which is explainable by local immunosuppression in the tumor bed. RIG‐I expression may inform checkpoint blockade and/or RIG‐I agonistic targeting in a subset of high‐risk OC patients., What's new? Previous evidence suggests that the antiviral helicase RIG‐I bears tumor‐suppressive activity. The clinical significance of RIG‐I in gynecological cancer remains unclear, however. This single‐center, retrospective, explorative biomarker study of 141 cases with epithelial ovarian cancer (OC) reveals the negative prognostic impact of RIG‐I. RIG‐I is overexpressed in OC tissue, particularly in the more aggressive type‐II OCs, and is an independent prognostic marker for overall survival. RIG‐I high‐expressing tumors carry an interferon signature, linking RIG‐I activation to a cancer microenvironment fostering tumor immune‐evasion including upregulation of immune checkpoints. RIG‐I expression may indicate high‐risk OC patients who may benefit from immunotherapeutic intervention.
Published: 2019
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23. Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study

Author: Dmitri, Nepogodiev, Joana Ff Simoes, Elizabeth, Li, Maria, Picciochi, James, C Glasbey, Glauco, Baiocchi, Ruth, Blanco-Colino, Daoud, Chaudhry, Ehab, Alameer, Kariem, El-Boghdadly, Funmilola, Wuraola, Dhruva, Ghosh, Rohan, R Gujjuri, Ewen, M Harrison, Herman, Lule, Haytham, Kaafarani, Mohammad, Khosravi, Irmgard, Kronberger, Sezai, Leventoğlu, Harvinder, Mann, Kenneth, A Mclean, Mengistu Gebreyohanes Mengesha, Maria Marta Modolo, Faustin, Ntirenganya, Lisa, Norman, Oumaima, Outani, Riinu, Pius, Peter, Pockney, Ahmad Uzair Qureshi, April Camilla Roslani, Sohei, Satoi, Catherine, Shaw, Aneel, Bhangu, Omar, M Omar, Waheed-Ul-Rahman, Ahmed, Leah, Argus, Alasdair, Ball, Edward, P Bywater, Amanpreet, Brar, Brett, E Dawson, Irani, Duran, Muhammed, Elhadi, Conor, S Jones, Sivesh, K Kamarajah, James, M Keatley, Samuel, Lawday, Ella, J Marson, Riinu, Ots, Irène, Santos, Elliott, H Taylor, Isobel, M Trout, Chris, Varghese, Mary, L Venn, William, Xu, Irida, Dajti, Arben, Gjata, Salah Eddine Oussama Kacimi, Luis, Boccalatte, Daniel, Cox, Philip, Townend, Felix, Aigner, Irmgard Elisabeth Kronberger, Elgun, Samadov, Amer, Alderazi, Kamral, Hossain, Greg, Padmore, Gabrielle van Ramshorst, Ismaïl, Lawani, Anis, Cerovac, Samir, Delibegovic, Gustavo Mendonça Ataíde Gomes, Igor Lima Buarque, Muhammad, Gohar, Mihail, Slavchev, Chukwuemeka, Nwegbu, Arnav, Agarwal, Janet, Martin, Joshua, Ng-Kamstra, Maricarmen, Olivos, Wenhui, Lou, Dong-Lin, Ren, Jose Andres Calvache, Carlos, J Perez Rivera, Ana Danic Hadzibegovic, Tomislav, Kopjar, Jakov, Mihanovic, Pablo Mijahil Avilés Jiménez, Nikolaos, Gouvas, Jaroslav, Klat, René, Novysedlák, Nicolas, Amisi, Peter, Christensen, Alaa, El-Hussuna, Sylvia, Batista, Eddy, Lincango-Naranjo, Sameh, Emile, Danilo Alfonso Arévalo Sandoval, Hailu, Dhufera, Samuel, Hailu, Mengistu, G Mengesha, Joonas, H Kauppila, Alexis, P Arnaud, Zaza, Demetrashvili, Markus, Albertsmeier, Hans, Lederhuber, Markus, W Löffler, Daniel Kwesi Acquah, Bernard, Ofori, Stephen, Tabiri, Symeon, Metallidis, Georgios, Tsoulfas, Maria-Lorena, Aguilera-Arevalo, Gustavo, Recinos, Tamás, Mersich, Dániel, Wettstein, Gabriele, Kembuan, Peiman Brouki Milan, Mohammad Hossein Khosravi, Masoud, Mozafari, Ahmed, Hilmi, Helen, Mohan, Oded, Zmora, Gaetano, Gallo, Francesco, Pata, Gianluca, Pellino, Yuki, Fujimoto, Naoto, Kuroda, Mohamad, K Abou Chaar, Faris, Ayasra, Ildar, Fakhradiyev, Intisar Hisham Said Hamdun, Jang, Jin-Young, Mohammad, Jamal, Lina, Karout, Aiste, Gulla, Fanjandrainy, Rasoaherinomenjanahary, Luc Hervé Samison, Iran Irani Durán Sánchez, Diana Samantha Gonzalez, Laura, Martinez, María José Martínez, Alejandra, Nayen, Antonio Ramos-De la Medina, Jade, Nunez, Pueya Rashid Nashidengo, Rakesh, Shah, Ashish Lal Shrestha, Pascal, Jonker, Schelto, Kruijff, Milou, Noltes, Pieter, Steinkamp, Deborah, Wright, Lukman, Abdur-Rahman, Adesoji, Ademuyiwa, Adewale, Adisa, Babatunde, Osinaike, Justina, Seyi-Olajide, Omolara, Williams, Emmanuel, Williams, Sofija, Pejkova, Zainab Al Balushi, Raza, Sayyed, Mustafa Abo Mohsen, Sadi, A Abukhalaf, Moises, Cukier, Hugo, Gomez-Fernandez, Sebastian Shu Yip, Ximena Paola Vasquez Ojeda, Marie Dione Sacdalan, Piotr, Major, José, Azevedo, Miguel, F Cunha, Ahmad, Zarour, Eduard-Alexandru, Bonci, Ionut, Negoi, Sergey, Efetov, Viktor, Kochetkov, Andrey, Litvin, Jc Allen Ingabire, Georges, Bucyibaruta, Ntirenganya, Faustin, Sosthene, Habumuremyi, Alphonsine, Imanishimwe, Haragirimana Jean de Dieu, Emmanuel, Munyaneza, Isaie, Ncogoza, Abdourahmane, Ndong, Dejan, Radenkovic, Min Hoe Chew, Frederick, Koh, James, Ngu, Arpád, Panyko, Uros, Bele, Jurij Aleš Košir, Hassan, Daoud, Ana Maria Minaya Bravo, Umesh, Jayarajah, Dakshitha, Wickramasinghe, Mohammed Elmujtba Adam Essa Adam, Martin, Rutegård, Malin, Sund, Michel, Adamina, Eleftherios, Gialamas, Karoline, Horisberger, Muhammad, Alshaar, Abel, Huang, Varut, Lohsiriwat, Shane, Charles, Haithem, Jlassi, Arda, Isik, Hervé Monka Lekuya, Slava, Kopetskyi, Hayder, Alsaadi, Sattar, Alshryda, Osaid, Alser, Brittany, Bankhead-Kendall, Kerry, Breen, Hassan, Mashbari, Fernando Bonilla Cal, Hamza, Al-Naggar, Mayaba, Maimbo, Dennis, Mazingi, Tom, Abbott, Melika, Akhbari, Ruth, Benson, Shivam, Bhanderi, Bruce, Biccard, Edward, Caruana, Sohini, Chakrabortee, Reema, Chapatwala, Ainhoa, Costas-Chavarri, Andreas, K Demetriades, Anant, Desai, Salomone Di Saverio, Thomas, Drake, John, Edwards, Jonathan, Evans, Marco, Fiore, Samuel, Ford, Christina, Fotopoulou, Alexander, Fowler, Kaori, Futaba, Ian, Ganly, Harelimana Grace James, Ewen, Griffiths, Alessandro, Gronchi, Peter, Hutchinson, Gabriella Yael Hyman, Joseph, Incorvia, Ritu, Jain, Michael, Jenkinson, Tabassum, Khan, Stephen Richard Knight, Angelos, Kolias, Søren, Kudsk-Iversen, Tsun Yu Kwan, Elaine, Leung, Julio, Mayol, Siobhan, Mckay, John, G Meara, Emily, Mills, Susan, Moug, Akshay, Patel, Roberto, Perinotti, Henry, E Rice, Keith, Roberts, Andrew, Schache, Richard, Shaw, Neil, Smart, Matthew, Stephens, Grant, D Stewart, Ella, Teasdale, Peter, Vaughan-Shaw, Raghavan, Vidya, Naomi, Wright, Natalie, Zimmelman, Ervis, Agastra, Dariel, Thereska, Sergio Martin Lucchini, Veronica, Laudani, Carina, Chwat, Ivana Ines Pedraza Salazar, Diana Alejandra Pantoja Pachajoa, Agustin, Duro, José Alfredo Calderón Arancibia, Giuliana, D'Aulerio, Nagendra, Dudi-Venkata, Natasha, Egoroff, Shebani, Farik, Natalie, Lott, Jana-Lee, Moss, Sarah, Rennie, Lorwai, Tan, Uyen Giao Vo, David, Watson, David, Watters, Tim, Bright, Paul, Hollington, Xuanyu, Zhou, Hidde, M Kroon, Anthony, Farfus, John, Barker, Eleanor, Watson, Sean, Stevens, Haider, Latif, Amanda Caroline Dawson, Alwin, Chuan, Vijayaragavan, Muralidharan, Enoch, Wong, Travis, Ackermann, Maurizio, Pacilli, Russell, Hodgson, Alexander, Heriot, Peter, Choong, Wendy, Brown, Surjit, Lidder, Justin, Yeung, Luke, Traeger, Guillermo, Regalo, Ralph, Gourlay, Sarit, Badiani, Cherry, Koh, Soni, Putnis, Fayza, Haider, Ashrarur Rahman Mitul, Niels, Komen, Bert, Dhondt, Serge, Cappeliez, Manon, Pigeolet, Martijn, Schoneveld, Jasper, Stijns, Wouter, Oosterlinck, Nicolas, Flamey, Cyrille, Kpangon, Mouhamed, Agbadebo, Sèmèvo Romaric Tobome, Aldo Vieira Barros, Samuel Aguiar Júnior, Heloisa Galvão do Amaral Campos, Jefferson, Gross, Felipe José Fernandez Coimbra, Luiz Paulo Kowalski, Fabiana, Makdissi, Suely, Nakagawa, Joao Pedreira Duprat Neto, Jose Guilherme Vartanian, Guilherme, Yazbek, Stenio, C Zequi, Ronald, Flumignan, Natalia, Jaworska, Angela, Dell, Harsha, Shanthanna, Abdollah, Behzadi, Carolyn, Nessim, Michelle, Mozel, Pascal, St-Germain, Crispin, Russell, Gary, Groot, Najib, Safieddine, Duminda, Wijeysundera, Antoine, Eskander, Sami, Chadi, Shawn, Mackenzie, Alana, Flexman, Fernando, Heredia, Julio, Villanueva, Sofia, Waissbluth, Roberto, Macchiavello, Mario, I Escudero, Tyare, Fuentes, Ximena, Mimica, Dinimo Bolivar Saenz, Lina, Caicedo, Juan Pablo Alzate, Joaquin, Luna, Nestor Fabian Pedraza Alonso, Camilo Ortiz Silva, Juliana, Rodriguez, Liliana, Silva-Igua, Martha Luz Torres, Lina María Trujillo, Albaro José Nieto Calvache, Julián, Balanta-Melo, Rafael, Figueroa-Casanova, Oscar-Julián, García-Montoya, Carlos Andres Marulanda Toro, Marcela Velez Botero, Maria Clara Mendoza Arango, Eneida Diaz Martinez, Valentina Gutiérrez Perdomo, Emileth, Montenegro, Julia, Rodriguez-Abreu, Dolores, Mejía, Galal, Abouelnagah, Sameh, Shehata, Ahmed Hossam Eldin Fouad Rida, Ramy, A Hassan, Mahmoud, M Saad, Mohamed Reda Loaloa, Badr, Mostafa, Mohamed, Qassem, Mohamed, Fahmy, Hesham, Abozied, Ahmed, Y Azzam, Sherief, Ghozy, Asser, Sallam, Ahmed, Shehta, Mohamed, Abdelkhalek, Rehab, Samaka, Amr, Morsy, Ahmed Elshawadfy Sherif, Abraham, Negussie, Tigist, Fisseha, Kibruyisfaw, Shumbash, Metasebia, Abebe, Seid Mohammed Yasin, Yemisirach Bizuneh Akililu, Abebe, Megersa, Teshome, Tefera, Melatework, Assefa, Bahru, Atnafu, Bereket, Tsegaye, Yoseph Solomon Bezabih, Silamlak, Sisay, Kebebe, Bekele, Moa, Jira, Habtamu, Derilo, Eyueal, Degefa, Anteneh, Tadesse, Melkamu, Nidaw, Elise, Sarjanoja, Sylvie, Testelin, Sophie, Boucher, Lionel, Jouffret, Zaher, Lakkis, Alban Zarzavadjian Le Bian, Luke, Harper, Marc Danguy des Déserts, Benoît, André, Karem, Slim, Romain, Verhaeghe, Andrea, Police, Edouard, Girard, Alexandre, Chebaro, Armande Subayi Nkembi, Laurent, Arnalsteen, Quentin, Ballouhey, Diane, Mege, Clement, Jeandel, Emilie, Duchalais, Pierre-Alban, Bouche, Gilles, Manceau, Célia, Crétolle, Erik, Hervieux, Noémie, Girard, Agathe, Seguin-Givelet, Sebastien, Gaujoux, Belinda De Simone, Matthieu, Boisson, Damien, Bergeat, Fabien, Fredon, Francesco, Nappi, Radwan, Kassir, Aurélien, Scalabre, Federico, Migliorelli, Anne-Cecile, Ezanno, Barbara, Seeliger, Charlotte, Vaysse, Helene, Charbonneau, Vincent, Misrai, Olivier, Abbo, Martina Aida Angeles, Laurent, Brunaud, Ali, Modabber, Sebastian, Wolf, Carsten, Kamphues, Philipp, Höhn, Tim, R Glowka, Alexander Christopher Rokohl, Ulrich, Bork, Georg, Fluegen, Raymund, E Horch, Andrea, Schmedding, Andreas, Schnitzbauer, Helge, Eberbach, Daniel, Schlager, Fritz, Spelsberg, Lena, Keppler, Andreas, Hecker, Susanne, Wolfer, Ulrich, Ronellenfitsch, Christine, Nitschke, Christian, Peiper, Ibrahim, Hakami, Stefan, Welter, Karine, Nikolaieva, Andreas, Roth, Judith, Lindert, Konstantinos, Gousias, Anke, Rissmann, Valerie Catherine Linz, Nuh, Rahbari, Marie-Claire, Rassweiler-Seyfried, Anna Eleonora Gut, Jens, Gempt, Daniel, Reim, Arthur, Wagner, Alexander, M Keppler, Mircea Gabriel Stoleriu, Tim, Saier, Josef, Stadler, Julia Christina Kaiser, Stefan, M Brunner, Karin, Pfister, Jonas, Herzberg, Kai, Nowak, Tobias, Reinhard, Gregor, A Stavrou, Alfred, Königsrainer, Christian, Konrads, Markus, Quante, Simon, Laban, Silke von Pusch, Markus, Hirschburger, Johannes, Doerner, Armin, Wiegering, Ekaterini Christina Tampaki, Alitza Gutiérrez Ruiz, Alejandra, Rodas, Ana Lucía Portilla, Jacqueline, Carrera, Amalia Barrios Duarte, Megan, Lowey, Sabrina, Barillas, Atul, Suroy, Dhaivat, Vaishnav, Raghunandan Gorantlu Chowdappa, Irappa, Madabhavi, Dhananjaya, Bhat, Sunil Kumar Venkatappa, Sumit, Thakar, Kavitha, Jain, Aruna, Kumar, Manoj, Nagar, Tushar, Mishra, Arunkumar, Sekar, Anand, Gupta, Lileswar, Kaman, Madhivanan, Karthigeyan, Manjul, Tripathi, Ashwin, Rammohan, Sudheer Othiyil Vayoth, Anupama, Rajanbabu, Anbukkani, Subbian, Rahul, Gupta, Monish, Raut, Nissi, Evelyn, R Lavanya Kannaiyan, Anil, Matai, Sanjeev, Misra, Vishal, Bhende, Sathish, Muthu, Indranil, Ghosh, Abhishek, Sharma, Ankur, Bajaj, Shiv, Rajan, Gaurav, Agarwal, Pranay, Pawar, Philip, Alexander, M Vijayakumar Vijayakumar, Zeeshan, Hameed, Badareesh, L, Navneet Kumar Chaudhry, Lipika, Baliarsing, Satish, Dharap, Amruta, Kulkarni, Yuvaraja, Thyavihally, Rahul Deo Sharma, S Pramesh, C, Rajesh, Soni, Surya Kumar Dube, Shilpa, Sharma, Harvinder, Singh, Lovenish, Bains, Rahul, Ghodke, Ashwani, Kumar, Vivek, Sodhai, Suvendu, Maji, Somprakas, Basu, Chandrashekhar, Mahakalkar, Ravi, Kannan, Asif, Mehraj, Ranganath, N, Ashish, Phadnis, Yadev, I, Alfie, Kavalakat, Rohin, Mittal, Karthik Chandra Vallam, Hamed, Akhavizadegan, Esmaeil Rezghi Maleki, Naser Yousefzadeh Kandevani, Hilary, Ikele, Catherine, Mcnestry, Christina, Fleming, Stephen, O'Brien, Sami Abd Elwahab, Niall, Davis, Mohsen, Javadpour, Brendan, Mcdonnell, Clare, O Connor, Jarlath, Bolger, Cillian, Clancy, Stefanie, M Croghan, Noel, Donlon, Carolyn, Cullinane, Ben, Creavin, Muheilan, Muheilan, Helen, Earley, Syed Mohammad Umar Kabir, Muhammad, Fahadullah, Éanna, Ryan, Tara, Connelly, Daisuke, Hashimoto, Majdi Ali Alqudah, Amer, Alajalen, Rand, Y Omari, Abdulrahman, Qasem, Yazan, Alawneh, Amer, Ahmad, Omar, Aladawi, Bourhan, Alrayes, Hanan, Haidar, Shatha, Husain, Faisal, Qassem, Adnan, Sumadi, Ala'a Abu Salhiyeh, Balqees Mahmoud Al-Manaseer, Zaid, Alsunna, Hazim, Ra'Ed, Faten Reyad Bani Hamad, Amro, Abuleil, Elmi Ahmed Mohamed Jimaale, Marah, Abu-Mehsen, Noor, Olaywah, Omar, Wafi, Hazim, Ababneh, Luai, Abu-Ismail, Almu'Atasim, Khamees, Ahmad, Alkhatib, Raikhan, Bolatbekova, Mukhtar, Kulimbet, Talgat, Nurgozhin, Timur, Saliev, Baurzhan, Zhussupov, Ydyrys, Almabayev, Dilyara, Kaidarova, Khalil, Tamoos, Ahmed, Aqeelah, Alsnosy Abdullah Khalefa Mohammed, Faraj Al Maadany, Ghadah, Alkadeeki, Milad, Gahwagi, Wafa, Aldressi, Mohamed, Amnaina, Arowa Hassan Abdulrahman Alansari, Akram, Alkaseek, Ghozlan, Yagoub, Anass Ben Amer, Marwa, Salem, Ayman, Almugaddami, Dania, Burgan, Mohammed, Abdelkabir, Khayriyah, Alshareef, Rayet Al Islam Ben Jouira, Ayman, Meelad, Ahmad, Bouhuwaish, Sumayya Essayah Dwaga, Houda, Khalifa, Bushray, Almiqlash, Taha, Suliaman, Mohammed, Alawami, Fras, Elhajdawe, Hajir, Aboazamazem, Ibrahim, Ellojli, Ahmed, Msherghi, Ismail Ali Saleh, Mohammed, Alayan, Marcel Didier Ndayishyigikiye, Akutu, Munyika, Philipp, Plarre, David, W Borowski, Cameron, Wells, Rebecca, Teague, Brodie, Elliott, David, Kieser, Omar, Mohyieldin, Nick, Mcintosh, Cheyaanthan, Haran, Jasmin, King, Jeong, Ha, Matthew James McGuinness, Opeoluwa, Adesanya, Julius, Olaogun, Akinola, Akinmade, Kefas, Bwala, Peter, Agbonrofo, Akinwale, Afolabi, Usang, Usang, Sebastian, Ekenze, Samson, Olori, Taiwo Akeem Lawal, Abiodun, Okunlola, Stephen, Kache, Danjuma, Sale, Lofty-John, Anyanwu, Chukwuma, Okereke, Musliu Adetola Tolani, Venko, Filipce, Lazar, Todorovic, Sotir, Stavridis, John George Massoud, Sareyah, Alsibai, Rizwan, Sultan, Humera Naz Altaf, Abu Bakar Hafeez Bhatti, Shahzad Hussain Waqar, Aliya, Aziz, Asad Ali Kerawala, Lajpat, Rai, Mariyah, Anwer, Aiman, Tariq, Bushra, Ayub, Sami Ullah Niazi, Muhammad Yasir Naseem, Muhammad Zeeshan Sarwar, Muhammad Imran Khokhar, Imdad Ahmad Zahid, Haroon Javaid Majid, Nabila, Talat, Muhammad, Asif, Muhammad Hamid Chaudhary, Umer, Farooq, Siddique, Ahmad, Waleed, Mabood, Syed Imran Bukhari, Muhammad, Tariq, Eesha, Yaqoob, Saad, Javed, Muhammad Usman Malik, Hassan Nawaz Yaqoob, Glenda Marina Falcon Pacheco, Robinson Mas Melendez, Arazzelly Del Pilar Paucar Urbina, Jose Rios Chiuyari, Carlos Eduardo Otiniano Alvarado, Lorena Fuentes Rivera Lau, Giuliano, Borda-Luque, Milagros, Niquen-Jimenez, Claudia, Arias, Sergio, Zegarra, Jenner Betalleluz Pallardel, Regina Amparo Ugarte Oscco, Gian, Mendiola, Yahaira Tatiana Carpio Colmenares, Carlos Shiraishi Zapata, Maria Rosa Ortiz, Filipe Castro Borges, Octavio, Viveiros, Pedro, Serralheiro, Paulo, Santos-Costa, Filipa, Mendes, Miguel Rocha Melo, Paulo, Cardoso, Ana, Soares, Rita Gonçalves Pereira, Nelson, Silva, André, Caiado, Maria Luís Sacras, Pedro, Azevedo, Rui, Almeida-Reis, João, Oliveira, Jorge, Nogueiro, Mafalda, Sampaio-Alves, Luciana Cidade Costa, Catarina, Baía, Ana Cláudia Deus, Rita, Branquinho, André, Marçal, André, Tojal, Silviu Tiberiu Makkai-Popa, Aurel, Mironescu, Florin, Grama, Elena Adelina Toma, Daniela, Filipescu, Nicolae, Bacalbasa, Natalia, Motas, Sebastian, Ionescu, Octav, Ginghina, Radu, Costea, Narcis Octavian Zarnescu, Radu, Drasovean, Mihail-Gabriel, Dimofte, Vlad, Porumb, Mikhail, Kirov, Yegor, Molitvin, Vadim, Pykhteev, Marianna, Raevskaya, Aleksandr, Butyrskii, Mushabab, Alshahrani, Azah, Althumairi, Nasser, Alzerwi, Ahmed Al Ameer, Tariq, Madkhali, Abddulrahman Saleh Almulhim, Salman, Ghazwani, Abdu, Ayoub, Othman, Iskander, Mohammed, Ghunaim, Mohammed, Alharthi, Turki, M Alzaidi, Mohammad, Alyami, Abdulrahman Al Amri, Abdullah, Alfakhri, Amal, Alhefdhi, Sharfuddin, Chowdhury, Thamer, Nouh, Ameen, Alshehri, Abdulrahman, Alzahrani, Yousef, Alalawi, Selmy, Awad, Ibrahima, Konate, Jacques, Tendeng, Nan Zun Teo, Sabra, Aqil, Cristina Barrena López, Ana Sánchez Mozo, Antonio Rodriguez Infante, Patricia Caja Vivancos, Mikel, Prieto, Igor Alberdi San Roman, Laura Gomez Fernandez, Josep Maria Muñoz Vives, Anna, Carreras-Castañer, Berta, Díaz-Feijoo, Ramon, Sieira-Gil, Victor, Turrado-Rodriguez, Anna Sánchez López, Santiago, Sánchez-Cabús, Marta Jimenez Toscano, MªPilar Canals Sin, Saura García Laura, Oriol Martin Sole, Pedro Palazon Bellver, Sonia, Pérez-Bertólez, Jordi, Prat-Ortells, Mireia Riba Martínez, Josep, Rubio-Palau, Xavier, Tarrado, Jorge, Nuñez, Veronica Alonso Mendoza, Coro, Bescós, Eloy, Espin-Basany, Martin, Espinosa-Bravo, Daniel, Gil-Sala, Susana, González-Suárez, Nuria Montferrer Estruch, Lucia Porteiro Mariño, Ana, Rodríguez-Tesouro, Fabian Rojas Portilla, M Pilar Tormos Pérez, Inmaculada, Vives, Unai Garcia De Cortazar, Kiara, Tudela, Aitor, Landaluce-Olavarria, Mercedes Estaire Gómez, Jorge, Almoguera, Bakarne, Ugarte-Sierra, Virginia, Jimenez, Marta, Bertrand, Laura Cárdenas Puiggrós, Olga, Delisau-Puig, Jorge, Garcia-Adamez, David Julià Bergkvist, Eloy, Maldonado-Marcos, Lucia Diego García, Marta Roldón Golet, Iván, Soto-Darias, Aida Cristina Rahy-Martín, Diego, Enjuto, Adolfo, Ramos-Luengo, Juan Delgado Fernandez, Carolina Lugo Duarte, Cristina Ojeda Thies, Lucila, Marquez, Diana Crego Vita, Jana, Dziakova, Jorge Caño Velasco, Olga, Mateo-Sierra, Begoña, Quintana-Villamandos, Cristina Rey Valcarcel, Javier, 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Amanda Lira Dos Santos Leite, Laercio, Pol-Fachin, Tainá Santos Bezerra, Alcimar Lavareda Dos Santos Junior Alcimar, Robson, Amorim, Maria Eduarda Bellotti Leão, João José Corrêa Bergamasco, Cintia Cardoso Pinheiro, Rubem Alves Da Silva Neto, Elaine Francisca De Araújo, Lilian, Guimaraes, Tatiana, Liborio-Kimura, Isabelle Melo da Camara, Victor Ripardo Siqueira, Juan, Rodriguez, Jeancarllo, Silva, Rubem Alves Silva Junior, Cláudio, Cardoso, Andre, Guimaraes, Wislene Sarajane Moreira Alves, Agna Soares Da Silva Menezes, Marcelo, Araujo, Kattiucy, Brito, Josie Marcelle Lira Albuquerque, Jairo Alberto Dussan-Sarria, Andressa, Souza, Andre Ricardo Stüker, Tiago, Bresciani, Luciana Cadore Stefani, Leandro Totti Cavazzola, Tainá, Costa, Matheus, Dasqueve, Gustavo De Bacco Marangon, Otávio Ritter Silveira Martins, Josy, Rodrigues, Guilherme Roloff Cardoso, Brasil Silva Neto, Tilaê, Soares, Aline, Zanella, Lucas Torelly Filippi, Enilde Eloena Guerra, Ricardo Pedrini Cruz, Antonio Nocchi Kalil, Gustavo, Laporte, Moacyr, Salem, Murilo de Lima Brazan, Caio Antonio de Campos Prado, Elaine Christine Dantas Moises, Hilda Satie Suto, Alice Gadotti Yasuda, Ana Carolina Tagliatti Zani, Roberto Cardoso Cardoso Dos Santos, Geraldo, Duarte, Edwaldo Edner Joviliano, Carolina Lourenço Gomes Dos Santos, Silvana Maria Quintana, Edwin, Tamashiro, Fabiana Cardoso Pereira Valera, Marília Veccechi Bijos Zaccaro, Isis, Andreotti, Leonardo, Lima, Wilson Salgado Jr, Alonço da Cunha Viana Júnior, Lana, Moutinho, Cora Pichler de Oliveira, Isabela Trindade Martins, Isabela Vieira Toledo, Marco Antonio Correa Guimaraes-Filho, Rodrigo, Arrivabeno, Claudio Bovolenta Murta, Danniel Frade Said, Jose Pontes Junior, Felipe Guimarães Pugliesi, Paulo, Gregorio, Alessandro, Mariani, Fabio, Minamoto, Juliana Lourenço da Silva, Bruno, Muller, Caio, Zanon, Vladimir, C Carvalho, Ana Lucia Munhoz Lima, Priscila, R Oliveira, Jorge Dos Santos Silva, Mariana Faccini Teixeira, Marco, Kulcsar, Leandro, Matos, Kamilla Schmitz Nunes, Joel Abdala Junior, Emne, Abdallah, Genival Barbosa Carvalho, Igor Correia de Farias, Cassia da Silva, Fabio Fernando Eloi Pinto, Luciana, Facure, André, Godoy, Bruna, Kupper, Fernanda, Leite, Matheus de Melo Lôbo, Henrique, Mantoan, Narimã, Marques, Tomas, Marques, João Paulo Medici, Silvio Melo Torres, Katheryne Merlos Garcia, Rafael Ribeiro Meduna, Ana Carolina Scintini Herbst, Silvana Soares Dos Santos, Bruna Tirapelli Gonçalves, Marcelo, Antonini, Carolina, Brienze, José Francisco Farah, Rodrigo, Gonçalves, Vinicius, Machado, Luis Roberto Nadal, Danilo Nadal Rodrigues, Adrieli, Pansani, Maria Luiza Rocha, Marcelo, Simonsen, Daniela, Tsuchiya, Rafaela, Vasques, Jorge, Amorim, Ana Alyra Carvalho, Rebeca, Correia, Brena Costa Dos Santos, Henrique Jorge Guedes Neto, Luis, Nakano, Mariana, Pereda, Vladimir, Vasconcelos, Jamile Barakat Awada, Guilherme, Gava, Tiago Riuji Ijichi, Nam Jin Kim, Rafael, Nunes, Fabio, Pinto, Thiago Henrique Sigoli Pereira, Gustavo Jardim Volpe, Arthur, Gatti, Caroline, Nardi, Ramon, Oliva, Layze Braz de Oliveira, Herica Emilia Félix de Carvalho, Ivonizete Pires Ribeiro, Gabriel Renan Soares Rodrigues, Álvaro Francisco Lopes de Sousa, Michel, Chebel, Paulo Henrique de Sousa Fernandes, Marcelo Augusto Faria Freitas, Juliano Rodrigues da Cunha, Zeenia, Ather, Dobromir, Dimitrov, Emil, Filipov, Elitsa, Gyokova, Ivelina, Ilieva, Tsvetomir, Ivanov, Martin, Karamanliev, Vasil, Neykov, Boyko, Atanasov, Nikolay, Belev, Paolina, Kamenova, Kaloyan, Tonev, Tsanko, Yotsov, Evguenia, Hristova, Kolyo, Spassov, Tsanko, Tsankov, Dragomir, Dardanov, Petar, Gribnev, Manol, Sokolov, James, Brown, John, Tanyi, Heather, Hurdle, Anthony, Maclean, Michael, Sander, Salim Al Riyami, Krittika, Bali, David, Bigam, Khaled, Dajani, Mehran, Anvari, Rafik, Bolis, David, Choi, Susan, Ellis, Michael, Gupta, Wael, Hanna, Dennis, Hong, Cynthia, Horner, Lea, Luketic, Peter, Moisiuk, Yaron, Shargall, Hilda, Alfaro, Nawar, Alkhamesi, Laura, Allen, Muriel, Brackstone, Eunice, Chan, Davy, Cheng, Jason, Chui, Nelson, Gonzalez, Brent, Lanting, S Danielle MacNeil, Robert, Mayer, Jacob, Mcgee, Mahesh, Nagappa, Nicholas, Power, Agya, Prempeh, Mehdi, Qiabi, Hassan, Razvi, Emil, Schemitsch, Herman, Sehmbi, Ushma, Shah, Yamini, Subramani, Edward, Vasarhelyi, Kelly, Vogt, Homer, Yang, Ali Ghorbani Abdehgah, Saba, Balvardi, Liane, Feldman, Julio Flavio Fiore Jr, Melissa, Hanson, Brent, Hopkins, Pepa, Kaneva, Lawrence, Lee, Julia, Leonard, Jad, Abou-Khalil, Andre, Martel, James, Stevenson, Susan, Lee, Richard, Merchant, Samuel, Avoine, Laurence, Belanger, Mathieu, Belanger, Etienne, Belzile, Anne-Sophie, Blais, Sofia, Boucher-Kovalik, Cindy, Boulanger-Gobeil, Etienne, Cardinal, Pierre-Olivier, Champagne, Jonathan, Cloutier, Simon, Corriveau-Durand, Mathieu, Cote, Maxime, Cote, Mathilde, Côté, Valérie, Courval, Suzanne, Demers, Christine, Desbiens, Mehdi El Ouazzani, Karine, Girard, Ève-Marie, Girard, Karo, Gosselin, Helene, Khuong, Nathalie, 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Philemon, Leung, Andrew, Lindberg, Juan Mata Gutierrez, Kelly, Mayson, Adam, Meneghetti, Drew, Phillips, John, Street, Carolina Carvajal Calderón, Daniel Alejandro Donoso Pizarro, Esteban, Fernández, Ángela, Molero, Nastassja, Mutarello, Jorge Núñez Lucic, Katherine Ochoa Gaete, Catalina Ruiz Lopez, Rina, Sepúlveda, Camila, Ulloa, Mauricio, Barreda, Matias, Dallaserra, Matías Günther Wood, Mauricio Sandoval Tobar, Francisco, Garcia-Huidobro, Jimena, Dona, Carolina Soto Diez, Daniel, Igor, Javier, Mena, José Tomás Reyes, Catalina Arredondo Soto, Jose, Campos, Javier, Gonzalez, Barbara, Rivera, Jaime, Altamirano-Villarroel, David, Cohn, Luis Marin de Amesti, Pedro, Recabal, Camilo, Sandoval, Bruno Catoia Fonseca, Monica, Contador, Andres, Hodali, Camila, Pincheira, Andrea Ramos Mantilla, Claudio Salas Garrido, Janina, Torres, Marco, Valenzuela, Zehua, Chen, Jiankun, Hu, Jin, Tao, Kun, Yang, Yuexin, Zhang, Yuan, Chen, Wang, Cunchuan, Wah, Yang, Xueli, Bai, Tingbo, Liang, Tao, Ma, Ning, Pu, Hanlin, Yin, Camilo, Caicedo, Diego Felipe Tellez Beltran, Alejandro, Escobar, Carolina Perez Granados, Lisbeth Alexandra Urueña Pinzon, Carlos, Bonilla, Diana, Santana, Oscar, Serrano, Andrea, Garcia, Fernando Giron Luque, Nasly, G Patino-Jaramillo, Laura Giselle Contreras Baquero, Nestor Augusto Muñoz Botero, Jhoana Andrea Murillo Castellanos, Andrea Juliana Vega Calvera, Lina, M Acosta Buitrago, Maria Paz Bohórquez-Tarazona, Paulo Andrés Cabrera Rivera, J Felipe Casas, Valeria Cormane Alfaro, Julian, Corso, Bayron, Guerra, Albert Franz Guerrero-Becerra, Akram Kadamani Abiyomaa, Felix Ramon Montes, Manuel Santiago Mosquera Paz, Camilo Andrés Polanía Sandoval, Natalia, Quintana, Carlos Fernando Roman Ortega, Carlos, Santacruz, Manuela, Téllez, Camilo Alejandro Velandia Sánchez, Fernando, Arias-Amézquita, Luis Felipe Cabrera Vargas, Natalia Cortes Murgueitio, Elkin, Escorcia, Kemel Ahmed Ghotme Ghotme, Jorge Luis Gomez-Mayorga, Alvaro Felipe Guerrero Vergel, Gabriel, Herrera-Almario, Eduardo, Londono-Schimmer, Juan, A Mejia, Guillermo, Monsalve, Camilo, Rodriguez, Juan Nicolas Rodriguez Niño, Luis Martín Rodríguez Ortegón, Daniel, Sanabria, Andres, Alvarez, Arnulfo, Andrade, Javier, Ardila-Montealegre, David, Baquero, Edgar Mauricio Barrios Vidales, María Alejandra Caicedo Giraldo, María Camila Carvajal, Maria, Castillo, Maria Carolina Castillo Florez, María Angelica Cendales, Danny Conde Monroy, Henry, Cortes, Mario, Daniel, Jairo De la Peña, Elena Leonor Delgado-Nieto, Hernando, Espitia, Carlos Figueroa Avendaño, Edgar Oswaldo Hernandez Burgos, Andres, Isaza-Restrepo, German, Londono, Margarita Maria Maldonado, Andrea, Montenegro, Juan Carlos Navarro, Jorge, Navarro-Alean, Katherine Parra Abaunza, Eliana, Pulido, Erika, M Ramírez Amaya, Carlos Eduardo Rey Chaves, Natalia Andrea Rivera Rincón, William Mauricio Riveros Castillo, Lizeth Rodriguez Sanchez, Wilson, Rubiano, Maria, Russi, Juan Carlos Sabogal Olarte, Javier Mauricio Salgado Tovar, Maria Juliana Sanchez, David Mauricio Solano Varela, Paula Torres Gomez, Marcial, Trillos, Ana María Vargas Patiño, Felipe, Vargas-Barato, Juan Pablo Villate Leon, María Alejandra Wagner Useche, Jesus, Acosta, Adriana, Almeciga, Luis Becerra Mendez, Rafael Jose Beltran, Ana, Bonilla, Miguel, Buitrago, Marino, Cabrera, Pedro Hernando Calderon Quiroz, Diego, Camacho-Nieto, Carlos Andrés Carvajal Fierro, Sergio Cervera Bonilla, Sandra, Diaz, Helena, Facundo, Jorge, Forero, Mauricio Garcia Mora, Karena Victoria Garcia Tirado, German Fabian Godoy Perez, Felipe, Gonzalez, Oscar, Guevara, Jairo Alonso Hernandez, David Ricardo Herrera Mora, Juan David Lalinde, Carlos, Lehmann, Eduardo Leon Llanos, Byron Eduardo Lopez De Mesa Lopez, Ivan, Mariño, Monica, Medina, Raúl Eduardo Pinilla Morales, Angela, Puerto, Andrea, Quintero-Ortíz, Juliana Rendón Hernández, Elio Fabio Sánchez Cortés, Alvaro Eduardo Sánchez Hernández, Raul, Suarez, Oscar, Suescun, Marco, Vanegas, Rodolfo, Varela, Jorge Luis Velez Bernal, David, Viveros-Carreño, Daniela Camargo Gómez, Angelica, Fletcher, Abel, Merchan, Euler Javier Burbano Luna, Indira, Cujiño, Mauricio Velasquez Galvis, Lina Maria Vergara Galliadi, Orlando Abonia Gonzalez Abonia Gonzalez, Maria Fernanda Acuna Saravia, Roberto, Arroyave, Jose Maria Barreto Angulo, Francisco Javier Bonilla-Escobar, Uriel, Cardona, Ivan Castañeda Giacometto, José Luis Castillo, Diego Fernando Castillo-Cobaleda, Diego Jose Caycedo Garcia, Brenda Marcela Coll Tello, Juan Carlos Dueñas-Ramirez, Oscar Andres Escobar Vidarte, Luis, Figueroa, Herney, Garcia-Perdomo, Alden, Gomez, Laura, Gomez, Alejandro, Gomez, Ana María Grande-Gil, David, Guarin, Natalia, Guzman, Enrique Herrera Castañeda, Marisol, Hinaoui, Anuar Armando Idrobo Escobar, Christian Kammerer Kammerer, Sergio, Leon, Carlos Antonio Llanos Lucero, Angie, López, Alexander Maximiliano Martinez-Blanco, Antonio José Montoya Casella, Ricardo Andres Niño Corredor, Sebastian, Ordoñez, Diego Alfredo Palta Uribe, 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Alvarez, Cesar David Galindo Regino, Angela Maria Giraldo Velasquez, Carlos Enrique Melo Moreno, Jorman, H Tejada, Jesus Hernan Tovar, German Alirio Tovar, Edison Alexander Benavides Hernández, Claudia Milena Orozco-Chamorro, Gustavo Adolfo Angel, Christian Ali Buesaquillo, Victor David Olave Montaño, Andrés, Sánchez-Gómez, Daniela Patricia Escalante Ureche, Jairo Martinez Garrido, Eben-Ezer, Genda, Fabrice, Eboma, Kristina, Bitunjac, Karlo, Grulović, Marijana, Vučković, Goran, Šantak, Emanuel, Borovic, Ana Bosak Versic, Damir, Hasandić, Natasa Poldan Grabar, Suzana Srsen Medancic, Lucija, Brkic, Sara, Cokarić, Petra Pavic Palac, Zeljka, Samac, Josipa, Tomić, Marija, Vrdoljak, Ivan, Bacic, Bernarda, Bakmaz, Nikolina Bratošević Vučičić, Domagoj, Brzic, Samir, Canovic, Emilio, Dijan, Maja Grgec Dragicevic, Robert, Karlo, Suzana, Konjevoda, Petra, Kovačević, Ivan, Kovačić, Frane, Markulić, Luka, Matak, Domagoj, Morović, Gordan, Perišić, Andrea, Simic, Neven, Skitarelić, Matea, Veršić, 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Ioanna, Pozotou, Olga, Stavrinidou, Anneza, Yiallourou, Lukáš, Burda, Michal, Dosoudil, Lubomir, Martinek, Wladyslaw, B Gawel, Milan, Lerch, Matúš, Peteja, Jan, Žatecký, Toman, Daniel, Martin, Formánek, Veronika, Javurkova, Markéta, Kepičová, Nicole, Macečková, Petr, Matousek, Ondrej, Simetka, Petr, Vavra, Karol, Zelenik, Jan, Černý, Sami, Khan, Robert, Lischke, Martin, Přibyl, Temoore, Younus, Yenuksha, Amarasena, Karel, Klíma, Setareh, Pirmorad, Zuzana, Hotová, Aleš, Mladěnka, Nulvin, Bozo, Julie Lykke Harbjerg, Louise, Hviid, Helle, Ø Kristensen, Mira, Mekhael, Mette Fugleberg Nielsen, Laerke, Paulsen, Saija, Sinimäki, Louise Zinck Mogensen, Peter, Bonde, Anders Lyng Ebbehøj, Anne-Sophie, Fenger, Aleksander Fjeld Haugstvedt, Christine Hangaard Hansen, Maria Lovisa Jönsson, Lars, N Jorgensen, Peter-Martin, Krarup, Anne-Louise, Lihn, Christian, Meyhoff, Helena, Otte, Anas Ould Si Amar, Henrik, Palm, Nis, Schlesinger, Henry, Smith, Ida, Tryggedsson, Anne Reiss Axelsen, Jens Kristian Baelum, Mark Bremholm Ellebaek, Signe Bremholm Ellebaek, Anders, Hogh, Maria, Acosta, Yancy, Acosta, Pedro, Baez, Luis Alfredo Betances, Luis Rodolfo Bonilla, Daniel, Cabreja, Wilton Cabrera Cruz, María Mabel Collado Expósito, Aldo, Crespo, Octavio, Cruz-Pineda, Claudio Samuel D'óleo García, Pedro, Díaz, Remberto, Escoto, Jatnna, Figueroa, Luis, Garcia, U Garcia-Dubus Rodriguez, Humberto, Gomez, Adrian, Grullon, Fatherin, Guerrero, Lillian, Guzman, Thelma Rocío Jiménez Mosquea, Engels, Lazala, Ariela, Lopez, Leeany Maletta Francisco, Jhomayri, Mercado, Herisardy, Munoz, Jeffrey, Paulino, Maricely Ambar Perez Fernandez, Rudeily, Reyes, Lilia Rosa Reyes Guilamo, Ruben, Rivas, Claudia Alejandra Rivas Torres, Ada, Rodríguez, Madelin Tamar Rosario Villa, Eleazar, Santana, Joel, Soto, Nassin, Tactuk, Cristina Kristel Tonos Sardiñas, Raul, Ubinas, Jose, Victoria, Aaron, Villegas, Ricardo, Acra-Tolari, Larissa, Beltran, Luis Fernand Betances, Alejandro, Blaubach, Denisse Idalia Campos Mejía, Nathalia, Capellan, María Fernanda Cedeño Bruzual, Saray Cordero Spencer, Gabriella Cuevas Lantigua, Luis De Jesus, Gabriela, Díaz, Pedro Pablo Díaz Vásquez, Karla, Disla, Jesús Antonio Echavarría Uceta, Paola Irina Eusebio Jimenez, Damaris, Fernandez, Marlin Fernandez Camilo, Jiomar Manuel Figueroa Germosen, Maruel, Fortunato, Leyla Gabriel Fernández, Alicia German Dihmes, Héctor, Herrera, Elizabeth Leon Cuevas, Jose Alejandro Mata, Mirian Mateo De La Cruz, Dolores Mejia De la Cruz, Marcos, Mirambeaux, Fabio Ortiz De La Cruz, Henry, Paulino, Gabriela, Pelletier, Merycarla, Pichardo, Rodriguez Pumarol Próspero Enrique, Julio, Rivas, Ann Stephany Sanchez Marmolejos, Roman Santana Santana, Irina Suero Almanzar, María Magdalena Vásquez Sánchez, Nicolás, Campuzano, José Ricardo Negrete Ocampo, Maria, Armas, Alvaro Santiago LeMarie Guerra, Gustavo León Vizcaya, Omar Ahmed Abdelwahab, Ahmed, O Elmehrath, Mohammed Ezzat Mostafa, Gamal, Amira, Ibrahim, Sallam, Mohamed, Sherief, Ahmed, 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Maher, Hosain, Ahmed, Hossam, Hamza Hussein Aly Salama Aly, Mohamed, Ibrahim, Abdelrahman, Ibrahim, Nourhan, Ibrahim, Noha Mohamed Salah Ibrahim Moussa Hamouda, Monica, Iskander, Islam, Khalifa, Mostafa, Kotb, Nada, Mahmoud, Alaa Mahmoud Abo Shabana, Nora, Mamdouh, Maram, Metwalli, Khaled, Metwally, Mahmoud, Moghazy, Moustafa, Mohamed, Mohamed, Mourad, Esraa, Moustafa, Kamilia, Mubarek, Nour Eldin Nader, Ahmed, Nasser, Samaa, Omar, Mostafa Shehata Qatora, Mohamed, Ragab, Marawan, Ragal, Dina, Ramadan, Rana, Ramadan, Sara, Ramadan, John, Romany, Ahmed, Sabry, Yasmeen, Said, Sara, Salamah, Ahmed Mostafa Saleh, Mona Saleh Mesbah Mohamed Elkaffas, Alaa, Salem, Hashem, Salim, Ahmed, Samih, Ahmed Samir Abdelaal, Ahmed, Shaheen, Yassmeen Sharafeldin Mohammed, Abdelrahman, Shehata, Mohamed, Shemeis, Karim, Shenit, Mennatallah, Sheta, Asmaa, Soffar, Yousef, Tanas, Ahmed, Tarek, Nermin, Yehia, Omar Khaled Mohamed Eid, Ammar Yasser Abdulfattah, Ahmed, Elsaghir, Mohamed Fouad Elganainy, Omar Ibrahim Elsayed, Omar, Elmandouh, Omar, Hamam, Mostafa Ahmed Shehata, Areej, A Abdelaziz, Ahmed, M Abbas, Wael Abd El-Ghani, Hossam Aldein, S Abd Elazeem, Mustafa Abd Elsayed, Ahmed Yassien Abd-Elkariem, Shimaa, Abdalla, Mahmoud, Abdel-Aleem, Khaled, Abdelazeem, Mahmoud, Abdelfattah, Mohammed, Abdelhafez, Mohamed, M Abdelkarem, Ali, Abdelraouf, Lamess, Abdullaha, Hossam, Abubeih, Moaiad Eldin Ahmed, Nagm Eldin Abu Elnga Ahmed, Ahmed, Ahmed, Sarah Ahmed Saad, Sherif, Alaa, Ali, Alhussaini, Abdelrahman Ahmed Abdelrahman Ali, Ibrahim, Ali, Wagdi, Ali, Mohamed Ali Mohamed, Mohamed, Ashraf, Muhammad, Bassiouni, Mohamed, G El-Adawy, Mohammad, El-Sharkawi, Hussein, Elkhayat, Khaled, Elmaghraby, Shady, Elsdfy, Mohamed, Elsharkawy, Almoutaz, Eltayeb, Mohamed Esmat Mohamed, Esraa, Essam, Mahmoud, Fahd, Osama, Farouk, Rabea, Gadelkareem, Ahmed, Ghoneim, Mohammed Hamada Takrouney, Ahmed, Hamdan, Abd El-Rahman Hamed, Ahmad, Hasan, Mohamed Abdelghafor Hassanin, Islam, Hawal, Kerollos, Henes, Mohamed Omar Herdan, Helal, F Hetta, Omar, Ibrahem, Mostafa, Ibrahim, Islam, H Ibrahim, Mahmoud, Kamel, Mohamed, Khallaf, Shrouk, M Elghazaly, Abobakr, Mahfouz, Osman, Mahmoud, Wesam, Mahran, Doha, Mahrous, Abadeer, Marsis, Ayman, Mohamed, Aliae Mohamed Hussein, Amr Mohamed Sayed, Mahmoud, M Mohammed, Ahmed, Mokhtar, Fatma, A Monib, Ahmed, Nageeb, Mariam Albatoul Nageh, Mohammed, Nageh, Nehal Gamal Omar, Abdelrahman, Ragab, Abdelrahman, Ramadan, Abdallah Rashad Temerik, Aya, Sabry, Hadeer, Safwat, Omar, Salah, Ahmed Elhussiny Salah Mahmoud, Ahmed, Saleh, Mahmoud, Sallam, Ahmed, Samir, Reem, Sayad, Esraa, Sayed, Ahmed, S Sedik, Mohammed, Shahine, Antonios, Soliman, Wael, Soliman, Mohamed Gamal Taher, Randa, Wanees, Ebrahim Ahmed Yousof, Ahmed, Youssef, Omar Zein Elabedeen, Ahmed Emad Sayed Hassan, Shrouk Abdel Fattah, Ahmed, Abostate, Samar, Ali, Saad Ali Saad Salama, Mohamed, Allam, Ahmed, Alsadek, Ebrahim, Arafa, Ahmed, Barakat, Mohammed El Sherpiny, Gehad, Elbehairy, Mahmoud, Eleisawy, 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David, Walawah, Makafui, Yigah, Safia, Yussif, Nuna, Jiagge, Emmanuel, Nachelleh, Jane, Acquaye, Kwabena, Agbedinu, Fareeda, Agyei, Akosua, Agyemang-Prempeh, Kwabena, Amo-Antwi, Michael, Amoah, George, Amoah, Yaw, A Amoako, Daniel Gyawu Aning, Frank, Ankobea-Kokroe, Dominic Annor Mintah, David, Anyitey-Kokor, Adu, Appiah-Kubi, Joshua, Arthur, Vincent, Ativor, Isaac, Barnor, Yasmine, Braimah, Regina, Darko-Asante, Anthony, Davor, Mohammed Duah Issahalq, Mawutor, Dzogbefia, Tano, Emile, Papa, Fiifi-Yankson, Valerie, Gaveh, Senyo, Gudugbe, Solomon, Gyabaah, Frank Enoch Gyamfi, Adam, Gyedu, Derrick, Gyimah, Bernard, Hammond, Boakye-Yiadom, Jonathan, Yorke, Joseph, Thomas Okpoti Konney, Anna, Konney, Kwasi, Kusi, Ishmael, Kyei, Agbenya, Lovi, Nuhu, Naabo, Boateng, Nimako, Beauty, Nyadu, Obed Ofori Nyarko, Ben Blay Ofosu-Barko, Philip Peprah Oppong, Anita, Osabutey, Martha, Poku, Robert, Sagoe, Abiboye, Yifieyeh, George, Ansong, Adam, Abass, Alhassan, Abdul-Mumin, Theophilus, Adjeso, John Abanga Alatiiga, Munira, Amadu, Nathaniel, Annan, German Azahares Leal, Mohammed, Bukari, Alexis, Buunaaim, Ernest, Cheyuo, Latif Daboo Salifu, Michael, Damah, Malcolm, Dery, Edem Kojo Dzantor, Odoniel Guerra Garcia, Yabasin Iddrisu Baba, Adamu, Issaka, Abdul-Jalilu Mohammed Muntaka, James, Murphy, Yaa Nyarko Agyeman, Wisdom Opoku Amankwaa, Imoro, Osman, Samuel, Pie, Anwar Sadat Seidu, Mohammed, Sheriff, Ana Maria Simono Charadan, Abraham, Titigah, Mundashiru, Yahaya, Musah, Yakubu, Edwin Mwintiereh Ta-Ang Yenli, Ioannis, Grypiotis, Nikolaos, Kiriakopoulos, Georgios, Koliopoulos, Vasilis, Kyvelos, Georgia, Micha, Triada, Papadopoulou, Dimitrios, Balalis, Evangelos, Fradelos, Dimitrios, Korkolis, Nicholas, Alexakis, Kyveli, Angelou, Dimitrios, Haidopoulos, Anastasia, Prodromidou, Alexandros, Rodolakis, Nikolaos, Thomakos, Dimitris, Psychogios, Pantelis, Antonakis, Konstantinos, Bramis, Leonidas, Chardalias, Ioannis, Contis, Nikos, Dafnios, Dionysios, Dellaportas, Papalouka, Dimitra, 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Liolis, Elias, Ioannis, Maroulis, Francesk, Mulita, Kerasia-Maria, Plachouri, Michail, Vailas, Charalampos, Doitsidis, Eva, Filo, Ioanna, Gkalonaki, Eleni, Kogia, Konstantina, Kontopoulou, Magdalini, Mitroudi, Christina, Panteli, Ioannis, Patoulias, Olga Ioulia Semkoglou, Dimitrios, Sfoungaris, Ioannis, Valioulis, Ioannis, Astreidis, Panagiotis, Christidis, Orestis, Ioannidis, Lydia, Loutzidou, Antonis, Mantevas, Konstantinos, Paraskevopoulos, Dimitris, Tatsis, Apostolos, Athanasiadis, Themistoklis, Dagklis, Ioannis, Kalogiannidis, Georgios, Kapetanios, Apostolos, Mamopoulos, Chrysoula, Margioula-Siarkou, Stamatios, Petousis, Ioannis, Tsakiridis, Christos, Anthoulakis, Chrysanthos, Christou, Antonios, Fantakis, Eirini, Iordanidou, Christos, Kaselas, Sousana, Panagiotidou, Vasileios, Papadopoulos, Kyriakos, Papavasiliou, Athanasios, Piachas, Ioannis, Siasios, Ioannis, Spyridakis, Theodoros, Theodoridis, Andreas, Tooulias, Eleftherios, Tsiridis, Maria, Tsopozidi, María, Alemán, Estuardo, Brolo, Ana Lucia Lemus, Jennifer, Greenberg, Krisna Mishel Morales Chew, José Rodrigo Oliva, María Alejandra De León Lima, Ismar Lopez Muralles, Felipe, Solares, Gaby, Ajcip, Claudia, Anton, Jose, Cojulun, Mario-Andrés, Flores, Noriega, José, Carlos Adolfo Marroquín Paiz, Steffanía, Morales, Ramiro, Najera, Eduardo Quiñónez Lorenzana, Pablo, Rivera, Lesly, Rodas, Victor, Santos, Dianne, Sosa, Natalia, Ybarra, José David Pérez Cajti, Carlos, Régil, Walter, A Osorio, Rember Rosales Arriola, Luis-Fernando, Talé-Rosales, Danilo, Herrera, Servio Tulio Torres Rodríguez, Sergio Alejandro Villeda, Joshua, Anicetti, Andrea Michelle Lowey Medina, Javier, Ardebol, Kathia, Barillas, Francis De Leon, Salvador, Recinos, Miguel-Angel, Marroquin-Alpirez, Yessica, Yax, Sophie, Hon, Yuk Ho Liu, Alex Qinyang Liu, Shirley, Liu, Hei Tung Natalie Chiu, Chi Man Tom Chow, Victor, Hau, Ho Wai Ip, Brian, Mak, Chung Ying Mok, Dennis, Ng, Yin Yu Eva Siu, Kiu Fung Wong, Jingya Jane Pu, Yu-Xiong, Su, Kit Ying Au-Yeung, David Yuen Chung Chan, Albert, Chan, Shannon Melissa Chan, Tsz Ching Chang, Tor Wo Chiu, Wang Kei Chiu, Zhexi, He, Man Fung Ho, Kevin Ki Wai Ho, Jacky Yan Kit Ho, Janet Wui Cheung Kung, Cheuk Ho Lam, Rainbow W, H Lau, Samuel Ka Kin Ling, Hon Ting Lok, Tony Wing Chung Mak, Chi-Fai, Ng, Simon, Ng, Kelvin Kwok-Chai Ng, Calvin S, H Ng, Michael Tim Yun Ong, Teresa, Tan, Sui Fan Tang, Jeremy Yuen-Chun Teoh, Anthony, Teoh, Bess Siu Yan Tsui, George Kwok Chu Wong, Randolph, Wong, Kwok Chuen Wong, Chi Hang Yee, Zsuzsanna, Antal, Attila, Kalman, Peter, Voros, Kiarash, Bahrehmand, Timea, Echim, Zoltan, Novak, Tamás, Sztipits, Laszló Ádám Bihari, László, Hidi, Laszlo, Piros, Balazs, Rózsa, Peter, Sotonyi, Lilla, Szatai, György, Herczeg, Bálint, Pordány, Fanni, Tornyi, Kristof, Dede, Tamás, Egyed, György, Saftics, Judit, Kulcsicka-Gut, Zsófia, Sipos, Dezso, Toth, Bhavin, Patel, Hardil, Majmudar, Saptak, Mankad, Sohilkhan, Pathan, Sharathkumarkl, L, Lokesh, Sasatti, Subramanyam, Mahankali, Santhosh Kumar Sampengere Annayappa, Tulika, Agrawal, Premkumar, Anandan, Aditya, Baindur, Manjunath, Bd, Savitha, C, S Anitha, G, Sandeep, Harigond, K Tejeswini, K, Venkatesh, Kesarla, Mallikarjuna, Manangi, B Hareesh, P, Jyothi K, R Ranjan, Athish, Shetty, Santhosh Shivashankar Chikkanayakanahalli, Tanvi, Sunil, Shreya, Syamala, Kavya, Tharanath, Aditya, Atal, Niranjana, Rajagopal, S Srinath, B, Vinod, Nk, L Thirumanikandan, P, Nitu, Mishra, Sushruta, Shrivastava, Rekha, Wadhwani, Reyaz, Ahmad, Zainab Ahmad Haq, Prateek, Behera, Ritika, Dhurwe, Rehan, Haq, Vaibhav, Jain, Anuj, Jain, Sunaina, Karna, Kameshwarachari, Pushpalatha, Sumit, Raj, John Ashutosh Santoshi, Pooja, Singh, Virendra, Verma, Vaishali, Waindeskar, Moorat Singh Yadav, Zaheda, Aziz, Koyel, Chakraborty, Preetam, Chappity, Gurudip, Das, Debajyoti, Datta, Saubhagya Kumar Jena, Madhabananda, Kar, Susanta, Khuntia, Pankaj, Kumar, Ravi, Kumar, Aswathi, Kv, Abhijeet, Mishra, Swastik, Mishra, Yash, Mittal, Dillip, Muduly, 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Somil, Jaiswal, Yashpal, Jaware, Navneet, Kala, Ruchi, Karnatak, Apjit, Kaur, Vijay, Kumar, Manoj, Kumar, Ambrish, Kumar, Upander, Kumar, Amit Kumar Shrivastava, Seema, Mehrotra, Brijesh, Mishra, Anand, Mishra, Namrata, Bal Krishna Ojha, Ahmad, Ozair, Uma Shanker Pal, Amita, Pandey, Nancy, Raja, Pooja, Ramakant, Ashutosh, Roy, Rekha, Sachan, Satyanarayan, Sankhwar, Pushp, Sankhwar, Divya, Sarin, Ayushi, Shukla, Sushil, Singh, Mohit, Singh, Kul Ranjan Singh, Renu, Singh, Uma, Singh, Urmila, Singh, Vandana, Solanki, Abhinav Arun Sonkar, Chhitij, Srivastava, Parijat, Suryawanshi, Vivek, Tewarson, Rajat, Verma, Manju Lata Verma, Awdhesh, Yadav, Gyan, Chand, K M, M Vishvak Chanthar, Dileep, Hoysal, Anjali, Mishra, Nitin, Batra, Arun, Bhatti, Rupali, Chopra, Shakina, David, Tapasya, Dhar, Uma Kant Dutt, Rohini, Dutta, Sumir, Gandhi, Parvez David Haque, B Paul Sudhakar John, Sreejith Kannummal Veetil, Gurvinder, Kaur, Navneet, Kumar, Anil, Luther, Anupam, Mahajan, Amit, Mahajan, Kavita, Mandrelle, Shefin, Mathews, Vishal, Michael, Partho, Mukherjee, Pinki, Pargal, Rajesh, Paul, Anupam, Phillip, Rachel, Phillips, Abhishek, Samuel, Noel, Singh, Inderjot, Singh, Abhijit, Singh, Sarvpreet Singh Grewal, Anusha, Singhania, Selven, Thirumalai, Ashish, Varghese, Joshua, Wesley, Josy, Thomas, Pradeep, Zechariah, Mariam Anjum Ifthikar, Rohan Thomas Mathew, Rohan, Shetty, M Vijayakumar Vijaykumar, Bm Zeeshan Hameed, Sufyan, Ibrahim, Gayathri, Jyothish, Sunil, Krishna, Stanley, Mathew, Arjun Suresh Kumar, Narinder, Singh, Piyush Kumar Sinha, Rachith, Sridhar, Sunny, Agarwal, Srikant, Balasubramaniam, Swati, Chhatrapati, Charulata, Deshpande, Ashni, Dharia, Sarita, Fernandes, Suraj, Gandhi, Mangesh, Gore, Abhilash, Jayakumar, Rameshwar, Mhamane, Anand, Nirgude, Sandesh, Parab, Manish, Patil, Amit, Peswani, Anjana, Sahu, Sarika, Samel, Fagun, Shah, Dipti, Haridas, Vijay, Shetty, Bejoy, Abraham, Varun, Agarwal, Quazi, Ahmad, Ashishkumar, Asari, Mohammad Ismail Attar, Nagaraja Sekhar Ayyalasomayajula, Sutej, Bachawat, Shivani, Bachhav, Vivek, Badhe, Sanjiv, Badhwar, Shubhabrata, Banerjee, Vikas, Basa, Vipul, Bothara, Somnath, Chattopadhyay, Sohin, Chaudhari, Rahul, Chavan, Priyank, Chawathe, Shailja, Dadhich, Anuj, Dalal, Avinash, Date, Mandar, Deshpande, Preetham, Dev, Niren, Dongre, Anirudha, Doshi, Maya, Gade, Shreyash, Gajjar, Mohan, Gawande, Amol, Ghalme, Bhavisha, Ghugare, Ishita, Gupta, Manoj, Jain, Divakar, Jain, Saumya Sekhar Jenasamant, Vaishali, Joshi, Vinay, Joshi, Neha, Kalwadia, Nandkishore, Kapadia, Hari Bipin Radhakrishnan Kattana, Tirathram, Kaushik, Akshat, Kayal, Shama, Kovale, Yogesh, Kulkarni, Abhaya, Kumar, Kranthi, Kumar, Kashmira, Kumawat, Vidyadhar, Lad, Namrata, Maskara, Rajesh, Mistry, Smruti Ranjan Mohanty, Kanchan, Motwani, Manoj, Mulchandani, Mandar, Nadkarni, Sanjay, Pandey, Mrunal, Parab, Dinshaw, Pardiwala, Amrita, Patkar, Neha, Pawar, Abhijit, Pawar, Abhinav, Pednekar, Vishal, Peshattiwar, Harshwardhan, Pokharkar, Ojas, Potdar, 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Reddy Voppuru, Anushri, Soni, Gira, Soni, Junaid, Alam, Dinesh, Bagaria, Minu, Bajpai, Akshay Kumar Bisoi, Arvind, Chaturvedi, Sandeep, Chauhan, Narendra, Choudhary, Rajendra Singh Chouhan, Sunil, Chumber, Kamran, Farooque, Vasubabu, Gudala, Amit, Gupta, Mohit, Joshi, Apoorva, Kabra, Shashank Sharad Kale, Abhinav, Kumar, Subodh, Kumar, Dhruv, Mahajan, Rajesh, Malhotra, P Ramesh Menon, Biplap, Misra, Samarth, Mittal, Rajinder, Parshad, Pratyusha, Priyadarshini, Sushma, Sagar, Pradeep Brijkishor Sharma, Vijay, Sharma, Vivek, Trikha, Mayank, Tyagi, Kuldeep, Bansal, Kalyan, Varma, Anurag, Mishra, Rajdeep, Singh, Rohit, Bhardwaj, Abhishek, Mittal, Sabarirajan, Ponnusamy, Gyan Ranjan Singh, Isha, Tuli, Pramod, Bhor, Sanjay, Dhar, Sachin, Kale, Manisha, Aggarwal, Himani, Gupta, Gurleen, Kaur, Ajinkya, Deshpande, Anup, Gadekar, Tanmay, Jaysingani, Taufiq, Panjwani, Rakesh, Patil, Narendra, Vaidya, Sunil Kumar Vishwakarma, Utkarsha, Wayal, Debnarayan, Dutta, Rajnish, Arora, Mohit, Dhingra, Pankaj Kumar Garg, Farhanul, Huda, Pankaj, Kandwal, Ravi, Kant, Rajkumar Kottayasamy Seenivasagam, Navin, Kumar, Shashank, Kumar, Lokavarapu Manoj Joshua, Radheyshyam, Mittal, Dharma Ram Poonia, Deepak, Rajput, Saravanan, Sadhasivam, Sudhir, Singh, Vivek, Singh, Kshitija, Chandanwale, Melissa, Philip, Vaibhav, Thorat, Yousuf, Choudhury, Devishmita, Das, Mautushi, Das, Subhadra, Goala, Farhana Yasmin Laskar, Parbin, Laskar, Kapil, Malik, Poulome, Mukherjee, Abhishek, Sarkar, S Thoibisana Singha, M Nongalei Singha, Damayanti, Singha, Gowtham, Srungavarapu, Ritesh, Tapkire, Siempui, Tling, Syed Muzamil Ishaq Andrabi, Gowhar Aziz Bhat, Nisar, Chowdri, Robindera, Kour, Fazl, Parray, Raahil, Shah, Zamir Ahmad Shah, Rauf, Wani, Soujanya, Adamala, Ravikanth, Gowder, Siddhi, Hegde, S Mashitha, M, Shreya, Sreeram, Sushil, Ankadavar, Darshan, Bafna, Bharat, Dhanani, Nikhil, Ingle, Piyush, Jadhao, Sinu, Joseph, Swapnil, Kapote, Shirin, Karkada, Parag, Lad, Rajan, Lohia, Suyog, Madje, Venkateshwaran, Narasiman, Meer, Chisthi, Gejoe, George, Harihara, Jothi, Dilber, Pareed, Godwin David, C Mathew, Livingston, Abel, Mansi, Agrawal, Rabindranath, B, Manish, Baldia, Ravi Kishore Barla, Manisha, Beck, Santosh, Benjamin, Jeremy, Bliss, Lisa, Cherian, Sreekar, Devarakonda, Geley, Ete, Arun Jacob Philip George, Amish, Gohil, Deeptiman, James, Mark Ranjan Jesudason, Lallu, Joseph, Treasa, Joseph, Kathir, Joyson, Gomathi, Karnan, Albert, Kota, Pushplata, Kumari, Anitha, Loganathan, Vasanth Mark Samuel, John, Mathew, Senthil, K Nathan, Joby Elizabeth Ninan, Ajay, Philip, R Priyadarshini Priyadarshini, Suganya, S, Habie, Samuel, Gilbert, Samuel, Daniel, Selvaraj, Srujan, Sharma, Suraj, Surendran, D Hariharan, T, Santhosh Kumar Thangaraj, Vinotha, Thomas, Varghese, Thomas, John, K Thomas, S Harish, Y, Manobhiram, Boggavarapu, Murali Krishna Voonna, Marilaeta Cindryani Lolobali, Christopher, Ryalino, Tjokorda Gde Agung Senapathi, Mahadewa, Tjokorda, I Made Gede Widnyana, Dita, Aditianingsih, Aino, Auerkari, Susilo, Chandra, Fachreza Aryo Damara, Mohammad Adya Firmansha Dilmy, Achmad Kemal Harzif, Sidharta Kusuma Manggala, Dedy, Pratama, Affan, Priyambodo, Andi Ade Ramlan, Ratna Farida Soenarto, Adhrie, Sugiarto, Ilham Utama Surya, Tamara, Tango, Aida Rosita Tantri, Raihanita, Zahra, Dedy, Fachrian, Andi, Hasyim, Ade, Susanti, Teddy, Saputra, Erwin, Syarifuddin, Andi Asadul Islam, Hendra, Pajan, Ahmad Hannan Amrullah, Khoirul, Anam, Thirza, Hadipranata, Julius Albert Sugianto, Aidyl, Fitrisyah, Mayang Indah Lestari, Nur Rachmat Lubis, Rizal, Zainal, Zulkifli, Zulkifli, Erick Gamaliel Amba, Warren, Lie, Andika Adiputra Thehumury, Tedy, Apriawan, Yunus Kuntawi Aji, Roidah Taqiyya Zahra Wathoni, Sumadi Lukman Anwar, Teguh, Aryandono, Wirsma Arif Harahap, Juni, Kurniawaty, Djayanti, Sari, Artanto, Wahyono, Yunita, Widyastuti, Akhmad Yun Jufan, Parisa, Arjmand, Mohammad, Etezadpour, Babak, Ganjeifar, Masoumeh, Hosseinpoor, Hassan, Mehrad-Majd, Mohsen, Rajati, Reza, Assadi, Ehsan, Noori, Parisa, Rajaei, Samira, Hajisadeghi, Mohammad, Mehdizadeh, Mina, Soltani, Narges, Alizadeh, Gholamreza Azarnia Azar Nia, Hamid, Heidari, Seyedmohamad Hosseini Zavareh Hosseini Zavareh, Ali Moazami Pour Moazami Pour, Farokh, Savaddar, Mostafa, Vahedian, Hoora, Amouzegar, Mojdeh, Bahadorzadeh, Seyedeh Homa Hemmasi, Ahmad, Kachoie, Ali Karimi Karimi, Sepideh, Miraj, Monireh, Mirzaie, Hossein Mokarami Mokarami, Amrollah, Salimi, Roghayyeh, Ahangari, Ali, Ahmadvand, Ali, Bashiri, Morteza, Borhani, Mohammad, Haidari, Mohammad Taghi Imani Khosroshahi, Shahrokh Jahan Bini, Mohsen, Koosha, Mohammad Kazem Moslemi, Ali, Naghibi, Shahrzad, Tehrani, Zahra, Yazdi, Seyyed Hassan Adeli, Majid, Alborzi, Hamed, Bagheri, Mohsen, Eshraghi, Hassan Fatemi Manesh, Mohammad, Ghomeisi, Seyed Fakhreddin Hejazi, Saeed, Madani, Nima Najafian Motahaver, Samieh, Norouzi, Mahdi Pezeshki Modarres, Ali, Shafiee, Jamshid, Vafaeimanesh, Hossein, Yusefi, Elahe, Hosseini, Pourya, Medhati, 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Marshall, Darya, Musa, Zeeshan, Ahmad, Emmet, Andrews, Bruno Chan Chin, Mark, Corrigan, Amy Edwards Murphy, Niamh, Foley, Padraig, Gardiner, Daniel, Hechtl, Michelle, Hsiao, Mohd Yasser Kayyal, Shane, Killeen, Maria, Lyons, Cathy, Burke, Matt, Hewitt, Marwa, Mohamed, Syeda Farah Nazir, Mei Yee Ng, Nor Azlia Abdul Wahab, Cathy, Monteith, Oladayo, Oduola, Lylas, Aljohmani, Timothy, Nugent, Paula, Corr, Lauren, Crone, Johnathon, Harris, Arnold, Hill, David, Kearney, Robert Anthony Keenan, Deirdre, Nolan, James, Ryan, Mark Philip Hehir, Carmen, Regan, Michael, Geary, Fergal, Malone, Claire, Mccarthy, Donal, B O'Connor, Shane, Considine, Emma, Donohoe, Caroline, Herron, John, Larkin, Thomas Hugh Lynch, Barry, Maguire, Rustom, Manecksha, Andrea Mc Carthy, Katharina, Nagassima, Erica, O'Sullivan, Pat, Rohan, Ryan, Roopnarinesingh, Salloum, Salloum, Thomas, Aherne, Mary, Barry, Gareth John Bowen, Ellen, Boyle, Joseph, Dowdall, Ann, Hanly, Ahmed, Hassanin, Helen, Heneghan, Conor, Hurson, Orlaith, Kelly, Rory, Kennelly, Aoife, Kiernan, Sean, T Martin, Nawar, Masarani, Damian, Mccartan, Enda, W McDermott, Ben, Murphy, Kin Cheung Ng, Nwabundo, Njeze, Aine, O'Neill, Ruth, S Prichard, Ned, Quirke, Ian Sean Reynolds, Des, Winter, Rowan, Casey, Mutaz, Elamin, Amy, Gillis, Dara, Kavanagh, Michael, Kelly, Áine, Mcnamee, Paul, Neary, Patrick, Owens, Akshaya, Ravi, Paul, Ridgway, Paul, Carroll, Chris, Collins, Amenah, Dhannoon, Amy, Fowler, Aisling, Hogan, Aoife, Lowery, Peter, Mcanena, Charlie, Timon, Stewart, Walsh, Wisam, Al-Ramli, Imran, Azeem, Muhammad Usaama Bahadoor, Zsolt, Bodnar, Hassan, Elmusharaf, Faisal Saeed Hassan, Adam, Hingum, Huilun, Huan, Seamus, Jennings, Mohamed Hamed Khalid, Mariya, Kuteva, Syed Nadeem Mujtaba, Shanell, Peeriyah, Hina, Rehman, Muhammad Assam Sarwar, Tony, Shaju, Ian, Stephens, Michael, Sugrue, Joseph, Thomas, Manvydas, Varzgalis, Saqib, Zeeshan, Alisha, Jaffer, Larne, Jones-Whiting, Colin, Peirce, Sean, Johnston, Seantee, Lim, Alwaleed, 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Massimiliano, Gennaro, Lorenzo, Giannini, Marcello, Guaglio, Marco, Guzzo, Andrea, Leva, Alberto, Macchi, Elena, Manzo, Fabio, Martinelli, Ilaria, Mattavelli, Vincenzo Maria Mazzaferro, Francesco, Raspagliesi, Luigi, Rolli, Laura, Sala, Roberto, Salvioni, Mario, Santinami, Silvia, Segattini, Luca, Sorrentino, Carlotta, Zaborra, Alexandre, Anesi, Gianmaria Casoni Pattacini, Mattia Di Bartolomeo, Francesca, Pecchini, Arrigo, Pellacani, Micaela, Piccoli, Federico, Fusini, Andrea, Gattolin, Marco, Migliore, Roberto, Rimonda, Diego, Sasia, Elisabetta, Travaglio, Federica, Brunetti, Marco, Cereda, Marco, Ceresoli, Luca, Cigagna, Cristina, Dell'Oro, Alessandro, Fogliati, Robert, Fruscio, Tommaso, Grassi, Maini Marzia Isabella, Luca Carlo Nespoli, Massimo, Oldani, Sara, Ornaghi, Nicolò, Tamini, Carmine, Antropoli, Antonio, Castaldi, Alessio, Palumbo, Gaia, Altieri, Umberto, Bracale, Francesco, Corcione, Marcello De Luca, Giovanni Domenico De Palma, Maria Michela Di Nuzzo, Ruggero, Lionetti, 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Matteo, Filardo, Marika Sharmayne Milani, Franco, Ragni, Andrea de Manzoni Garberini, Edoardo, Baldini, Diana, Carpaneto, Michele, Cauteruccio, Corrado, Ciatti, Luigi, Conti, Serena, Gattoni, Pietro, Maniscalco, Gerardo, Palmieri, Calogero Puma Pagliarello, Giuseppe, Caristo, Raffaele, Galleano, Michele, Malerba, Marcello, Calabrò, Francesca, Farnesi, Elia Giuseppe Lunghi, Andrea, Muratore, Nicoletta Sveva Pipitone Federico, Joel Reuben Abel, Lorenzo, Andreani, Darienzo, Antonio, Vittorio, Aprile, Riccardo, Balestri, Giacomo, Benettini, Stefano, Berrettini, Luca, Bruschini, Massimo, Chiarugi, Federico, Coccolini, Simone, Colangeli, Camilla, Cremonini, Lodovica Cristofani Mencacci, Iacopo, Dallan, Silvia De Santi, Gregorio Di Franco, Lorena Di Girolami, Giacomo, Fiacchini, Niccolò, Furbetta, Stylianos, Korasidis, Marco, Lucchi, Andrea, Morandi, Luca, Morelli, Serena, Musetti, Carlo Maria Neri, Matteo, Palmeri, Miriana, Picariello, Francesco, Porcelli, Marco, Puccini, Nicolo, Roffi, Erica, Statuti, Dario, Tartaglia, Alberto, Tonelli, Matteo, Vianini, Gianluca, Baronio, Mauro, Montuori, Enrico, Pinotti, Stefano Maria Massimiliano Basso, Federica, Maffeis, Paolo, Ubiali, Lorenzo, Aguzzoli, Saverio, Coiro, Giuseppe, Falco, Vincenzo Dario Mandato, Valentina, Mastrofilippo, Simone, Mele, Caterina, Baldi, Carlo, Corbellini, Gianluca Matteo Sampietro, Massimo, Dugo, Mauro, Garino, Chiara, Marafante, Antonio, Masciandaro, Elisabetta, Moggia, Alessandra, Murgese, Felice Eugenio Agro, Gabriella Teresa Capolupo, Filippo, Carannante, Marco, Caricato, Vincenzo, Denaro, Erica, Mazzotta, Rocco, Papalia, Giuseppe, Pascarella, Alessandro, Strumia, Biagio, Zampogna, Matteo, Cinquepalmi, Marco, Colasanti, Celeste Del Basso, Federica, Falaschi, Nicola, Guglielmo, Roberto Luca Meniconi, Alessandra, Pecoraro, Sofia, Usai, Giacomo, Crescentini, Antonella, Larcinese, Emanuele, Picone, Giovanni, Sinibaldi, Annamaria, Agnes, Salvatore, Agnes, Sergio, Alfieri, Francesco, Belia, Valentina, Bianchi, Giuseppe, Bianco, Alberto, Biondi, Paola, Campennì, Valerio, Cozza, Sabatino, D'Archi, Domenico, D'Ugo, Veronica De Simone, Marta Di Grezia, Sofia Di Lorenzo, Federica, Ferracci, Valeria, Fico, Gianluca, Franceschini, Pietro, Fransvea, Giulio, Gasparini, Luca, Gordini, Antonio La Greca, Francesco, Litta, Celestino Pio Lombardi, Angelo Alessandro Marra, Angelo, Parello, Marco Maria Pascale, Romeo, Patini, Gilda, Pepe, Roberto, Persiani, Caterina, Puccioni, Carlo, Ratto, Fausto, Rosa, Gianmarco, Saponaro, Lorenzo, Scardina, Tedesco, Silvia, Giuseppe, Tropeano, Maria, Benevolo, Daniele, Bugada, Flaminia, Campo, Maria Gabriella Dona, Valentina, Manciocco, Paolo, Marchesi, Riccardo, Mastroianni, Francesco, Mazzola, Silvia, Moretto, Raul, Pellini, Gerardo, Petruzzi, Barbara, Pichi, Giuseppe, Simone, Gabriele, Tuderti, Jacopo, Zocchi, Luigi Marino Cosentino, Andrea, Sagnotta, Roberta, Angelico, Vittoria, Bellato, Michela, Campanelli, Marzia, Franceschilli, Michele, Grande, Giorgio, Lisi, Tommaso Maria Manzia, Lorenzo, Petagna, Bruno, Sensi, Giuseppe, Sica, Leandro, Siragusa, Giuseppe, Tisone, Marco, Assenza, Barbara, Binda, Massimo, Biondi, Gioia, Brachini, Placido, Bruzzaniti, Mauro, Casagrande, Flavia, Ciccarone, Pierfranco Maria Cicerchia, Bruno, Cirillo, Daniele, Crocetti, Giancarlo, D'Ambrosio, Vito, D'Andrea, Francesca De Felice, Giorgio De Toma, Carlo Della Rocca, Giulia, Duranti, Pietro, Familiari, Enrico, Fiori, Giovanni Battista Fonsi, Alessandro, Frati, Stefania La Rocca, Filippo La Torre, Pierfrancesco, Lapolla, Giovanni, Marruzzo, Simona, Meneghini, Andrea, Mingoli, Andrea, Picchetto, Antonella, Polimeni, Diego, Ribuffo, Maurizio, Salvati, Antonio, Santoro, Paolo, Sapienza, Luigi, Simonelli, Valentino, Valentini, Martina, Zambon, Giuseppa, Zancana, Emma, Zuppi, Simone, D'Annunzio, Cosimo De Nunzio, Silvia, Fiorelli, Mohsen, Ibrahim, Chiara, Loffredo, Domenico, Massullo, Cecilia, Menna, Rocco, Monica, Massimiliano, Pelli, Erino Angelo Rendina, Leonardo, Teodonio, Andrea, Tubaro, Giulio, Argenio, Giulio, Accarino, Accarino, Giancarlo, Antonio Nicola Giordano, Luca, Cardinali, Elisa, Sebastiani, Grazia, Travaglini, Erika, Andreatta, Emanuele Luigi Giuseppe Asti, Daniele, Bernardi, Luigi, Bonavina, Caterina, Froiio, Andrea, Lovece, Chiara, Copelli, Alfonso, Manfuso, Pasquale Di Maio, Marco, Giudice, Oreste, Iocca, Rosario, Cennamo, Tommaso, Cornali, Francesco Di Marzo, Cristian, Altana, Francesco, Bussu, Giampiero, Capobianco, Anna Giacomina Carta, Sandro, Ciccarello, Maria Laura Cossu, Pietrina, Cottu, Giacomo De Riu, Salvatore, Dessole, Francesco, Dessole, Salvatora, Dettori, Carlo, Doria, Alessandro, Fancellu, Claudio, F Feo, Giorgio Carlo Ginesu, Giuliana, Giuliani, Marco Giuseppe Iannuccelli, Massimo, Madonia, Roberto, Mancino, Olindo, Massarelli, Gianfranco, Meloni, Fabio, Milia, Andrea, Mulliri, Teresa, Perra, Marco, Petrillo, Antonio, Piras, Franco, Piredda, Francesco, Pisanu, Alberto, Porcu, Davide, Rizzo, Angelino, Sanna, Antonio Mario Scanu, Fabrizio, Scognamillo, Damiano, Soma, Anna Rita Tanca, Alessandro, Tedde, Matteo, Tedde, Luigi Angelo Vaira, Andrea Bartalini Cinughi de Pazzi, Osvaldo Carpineto Samorani, Daniele, Fusario, Luigi, Marano, Gaia, Oldrà, Anna Lisa Pesce, Stefania Angela Piccioni, Luca, Resca, Vincenzo, Ricchiuti, Franco, Roviello, Vinno, Savelli, Alberto, Abrate, Pierpaolo, Bordoni, Lorenzo, Bosio, Guglielmo, Clarizia, Francesco, Fleres, Marco, Franzini, Antonio, Fratto, Pierluigi, Giumelli, Alessandro, Grechi, Alessandro, Longhini, Fabrizio, Lorusso, Elisa, Scarnecchia, Federica, Scolari, Alessandro, Spolini, Vincenzo, Maiuri, Matteo, Papandrea, Arturo, Roncone, Lorenzo, Conti, Andrea, Rizzi, Marco, Rovagnati, Alberto, Brolese, Tommaso, Cai, Francesco Antonio Ciarleglio, Francesca, Dalprà, Gianni, Malossini, Liliana, Mereu, Irene, Tamanini, Saverio, Tateo, Giovanni, Viel, Enrico, Battistella, Paolo Boscolo Rizzo, Cristoforo, Fabbris, Marco, Massani, Giacomo, Spinato, Roberta, Tutino, Ugo, Grossi, Alessandro, Iacomino, Simone, Novello, Maurizio, Romano, Serena, Rossi, Giulio, Santoro, Giacomo, Zanus, Sokol, Trungu, Giada, Aizza, Gabriele, Bellio, Selene, Bogoni, Marina, Bortul, Biagio, Casagranda, Sara, Cortinovis, Nicolò de Manzini, Davide, Drigo, Paola, Germani, Manuela, Mastronardi, Lucia, Paiano, Silvia, Palmisano, Pier Luigi Filosso, Francesco, Guerrera, Matteo, Marro, Mauro, Rinaldi, Enrico, Ruffini, Stefano, Salizzoni, Laura, Bardelli, Mattia, Berselli, Giacomo, Borroni, Eugenio, Cocozza, Matteo, Desio, Bottazzoli, Elisa, Giuseppe, Ietto, Valentina, Iori, Domenico, Iovino, Lorenzo, Livraghi, Valentina, Marchionini, Stefano, Megna, Emma Amal Nahal, Mara, Palumbo, Valeria, Quintodei, Alessandra, Zullo, Lucrezia, D'Alimonte, Giovanni, Pirozzolo, Chiara, Vignotto, Tommaso, Campagnaro, Andrea, Caravati, Simone, Conci, Carlotta De Cristofaro, Gabriele, Gecchele, Tommaso, Giuliani, Jacopo, Graziosi, Alfredo, Guglielmi, Salvatore, Paiella, Corrado, 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Rakotoarisoa, Maharo, Ramifehiarivo, Solonirina Harinarindra Ranaivoson, Hajamihamina Marina Parfaite Randriantsoa, Narindra Njarasoa Mihaja Razafimanjato, Jeannie Ba Razafindrahita, Solofoarimanana, Solofoarimanana, Guillaume Odilon Tsiambanizafy, Rakotonaivo Mamisoa Judicaël, Corinne Eulalie Solo, Tojomamy Herinjaka Ralaizafindraibe, Fanonjomahasoa Safiry Andofenohasina, Hanta, Rasataharifetra, Vanona Barijaona Razafindraibe, Angelin Sablon Herinirina, Andre, Das, Thanga, Ganapathy, Yohesuwary, Gunarasa, Kalyani, Mariapan, Maathichsudhaar, Muniandy, Mohd Firdauss Osman, Mohd Azem Fathi Mohammad Azmi, Jien Yen Soh, Wan Zainira Wan Zain, Andee Dzulkarnaen Zakaria, Zaidi, Zakaria, Kheng Hooi Chan, Firdaus, Hayati, Syamim, Johan, Jin Jiun Mah, Ratha Krishnan Sriram, Sentilnathan, Subramaniam, Nur Shahirah Binti Muhammad Shahimi, Khairul Hazim Hamdan, Mohd Razali Ibrahim, Guhan, Muthkumaran, Ju Ann Tan, Mohana Raj Thanapal, Dayang Anita Abdul Aziz, Mae-Lynn, Bastion, Mohd Hairul Nizam Harun, Farrah-Hani, Imran, Norshamsiah Md Din, Ayesha Mohd Zain, Mushawiahti, Mustapha, Syed, Nabil, Ainal Adlin Naffi, Abd Jabar Nazimi, Roszalina, Ramli, Bee Hong Soon, Pavin, Bal, Joo Qing Cheng, Mohd Rusdi Draman, Ahmad Nazran Fadzli, Sakina, Ghauth, Weipin, Hung, Suniza, Jamaris, Peng Soon Koh, Sivakumar, Krishnasamy, Yeong Sing Lee, Yew Toong Liew, Jeffery Zk Lim, Raymond Chung Siang Lim, Hiong Chin Lim, Siti Farhan Moh Pauzi, Shireen Anne Nah, Ashvin Krishna Nair, Doris Sin Wen Ng, Yuki Julius Ng We Yong, Kamarajan, Ramayah, Rahmah, Saaid, Anand, Sanmugam, Mee Hoong See, Kanesh Kumaran Seevalingam, Neha, Sethi, Srihari, Singaravel, Syeda Nureena Syed Jafer Hussain Zaidi, Chu Yik Tang, Li Ying Teoh, Kian Boon Wong, Ruben, Xavier, Ahmad Shuib Yahaya, Norhafiza, Ab, Rahman, Islah Munjih Ab, Rashid, Mohd Fahmi Abd Aziz, Mohd Norhisham Azmi Abdul Rahman, Nasser Muhammad Amjad, Shahidah Che Alhadi, Faisal, Elagili, Mohd Nazli Kamarulzaman, Azmi Md Nor, Ahmad Faidzal Othman, Mohd Yusof Sainal, Mat Salleh Sarif, Richelle, Chua, Aini Fahriza Ibrahim, Abdul Rauf Bin Ahmad, Yii Ling Lau, Ka Yee Liew, Kandasami, Palayan, Hui Yu Wong, Jasiah, Zakaria, Nor Azimah Abd Aziz, Norazila Abdul Rahim, Noorneza Abdul Rahman, Bahiyah, Abdullah, Mohamed Faizal Bin Sikkandar, Fatin, Firman, Nik Mohd Hazleigh, Intan Kartika Kamarudin, Shahril, Khalid, Mohd Fairudz Mohd Miswan, Akmal Zulayla Mohd Zahid, Norasyikin, Mustafa, Kadhim, Obaid, Mohd Yusoff Bin Yahaya Yahaya, Ahmad Ramzi Yusoff, Predrag, Andrejevic, Jeremy Borg Myatt, Svetlana, Brincat, Clifford, Caruana, Kurt Lee Chircop, Francesca, Chircop, Daniel Mario Chircop, Charles, Cini, Viktoria, Czok, Melanie, Farrugia, Gabriella, Grima, Fatimah Mj Hassan Almukhariq, Esther, Muscat, Darryl, Pisani, Mohsin Hassan Khan Roshan, Nicholas, Schembri, Mohamed, Shoukry, Neville, Spiteri, Gilbert, Tanti, Ziad Aboharp Hasan, Alberto Bazan Soto, Cedillo Rodrìguez Jonathan Rubén, Gustavo Esteban Lugo Zamudio, David Gerardo Miranda Gómez, José Alfredo Pérez Meave, Victor Pinto Angulo, Antonio Rojas Aguilar, Erik Efrain Sosa Duran, Alejandro Vàzquez Perez, Diego, Arroyo, Jose, Corona-Cruz, Hector, Martinez-Said, Heriberto, Medina-Franco, Manuel, Mendez, Teresa Moreno, Y Suárez Ma, Dolores Orta Díaz, Martha Patricia Pérez de León Vázquez, Angélica Azucena Soto Carvajal, Fidel Soto Hernández, Juan Ignacio Stenner, Adriana Valenzuela López, Mauricio Rene Hernandez, Rey Jesus Romero, Aldo Bernal Hernandez, Ana Olivia Cortes-Flores, Carlos Jose Zuloaga Fernandez Del Valle, Carlos Andres Colunga Tinajero, Jaime, Orozco-Perez, Laura Gabriela Peña Balboa, Guillermo, Yanowsky-Reyes, Víctor Hugo Alcalá Torres, Francisco José Barbosa Camacho, Irma Valeria Brancaccio Perez, Miguel Angel Calderon-Llamas, Aldo Camacho Gomez, Edgar-Joaquin, Cortes-Torres, Esteban, Cueva-Martinez, Oscar Durán Anguiano, Isaac Esparza Estrada, Roberto, Fierro-Rizo, Paola Flores Becerril, Clotilde Fuentes Orozco, Miguel García Castillo, Alejandro Gonzalez Ojeda, Ana Sofia Gonzalez Rubio, Erick Alonso González-García de Rojas, Luis Humberto Govea-Camacho, Jose Aldo Guzman Barba, Juan Carlos Ibarrola Peña, César Íñiguez Martínez, Francisco Javier Llamas-Macias, Ruben Eduardo Morán Galaviz, Cesar, Nuño-Escobar, Oscar-Everardo, Olvera-Flores, Jaqueline, Osuna-Rubio, Jose Victor Pérez-Navarro, Rodrigo, Prieto-Aldape, Luis Ricardo Ramirez Gonzalez, Marco Vinicio Ramírez Sánchez, Emilio, Reyes, Olaya Moramay Romero-Limón, Carlos Beas Ruiz-Velasco, José Antonio Sánchez Martínez, Guillermo, Sanchez-Villaseñor, Ismael, Sedano-Portillo, Gabriela Ambriz Gonzalez, Pedro Berrones Moreno Berrones Moreno, Ana Beatriz Calderon Alvarado, José de Jesús Cárdenas Barón, Araceli, Hernández, Francisco Javier León Frutos, Edgard Efren Lozada Hernandez, Eduardo Morales Valencia, Karla Daniela Pérez, Francina, Bolanos-Morales, Julio, Herrera-Zamora, Patricio, Santillan-Doherty, David Omar Arriaga Zavala, Salvador Francisco Campos Campos, Lizette, Carmona, 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Alexander, Borgstein, Suzanne, Gisbertz, Sarah, Mikdad, Mark van Berge Henegouwen, Roel, Bakx, Marc, Besselink, Daniel Hl Lemmers, Anne-Jasmin, Roelofs, Paul van Amstel, Claire van Helsdingen, Ludi, Smeele, Niels, Harlaar, Frederik, Jonker, Sjirk van der Burg, Justin, Y van Oostendorp, Saranda, Ombashi, Tim van der Voort, Martijn van Geldorp, Lisanne, Posma-Bouman, Hans Donald de Boer, Annette, Olieman, Henriette, Smid-Nanninga, Jean-Paul P, M De Vries, Rianne, Hogenbirk, Tyche, Derksen, Josephine, Franken, Steven, Oosterling, Peter, Nolte, Jelle van der List, Ian, Alwayn, Okker, Bijlstra, Andries, Braat, Ruth, Bulder, Michèle de Kok, Robin, Faber, Ben, Goudsmit, Jaap, Hamming, Sven, Mieog, Alexander, Vahrmeijer, Fenna E, M van de Leemkolk, Joost van der Vorst, Jan van Schaik, Merel, Verhagen, Kim, Albers, Larsa, Gawria, Harry Van Goor, Michiel, Warle, Tessa, M van Ginhoven, Charlotte, Viëtor, Evert-Jan, Boerma, Lara, Lallitsch, Donald, Schweitzer, Wouter, Leclercq, Julie, Sijmons, 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Asensio, Luis Asensio Gomez, Diego, Carrion, Nuria, Chavarrias, Alvaro de Arriba, Jose Antonio Gazo Martínez Gazo, Alberto Gegúndez Simón, Juan Gómez Rivas, Natalia Gonzalez Alcolea, Carolina, Gonzalez-Gomez, Sara Gortázar de Las Casas, María Alexandra Heras Garceau, Alicia Hernández Gutierrez, Luis, Lassaletta, Fuad Samir Lopez Fernández, Marta, Mancheño, Blanca, Mateos-Serrano, Isabel Pascual Miguelañez, Maria Fernanda Pedrero Escalas, Julio, Peñarrocha, Yolanda, Perez, Maria Isabel Prieto-Nieto, Teresa Rivera Schmitz, Laura, Rodrigáñez, Ines, Rubio-Perez, Isabel Sanchez Cuadrado, José Ignacio Sánchez Méndez, Jorge Fernando Tone, Carlos Toribio Vazquez, Aitor, Urbieta, Diego Córdova García, Francisca Garcia-Moreno Nisa, Laura, Jiménez, Inmaculada, Lasa, Belen, Matías-García, Fernando, Mendoza-Moreno, Marina Pérez González, Ana Sánchez Gollarte, Alejandro Sanchez Pellejero, Cristina Vera Mansilla, Rafael, Barberá, Lourdes, Montes-Jovellar, Sara Fra Fernández, Nicolas Moreno Mata, Barbara, Algar-Yañez, Gutiérrez, Bérénice, Olga De La Varga-Martínez, Paula, Fernandez-Valdes-Bango, Sandra Maria Gadin-Lopez, José María Martínez-Gómiz, Elena, Nieto-Moreno, Ana, Nieto-Moreno, Montserrat Ocampos Hernandez, Maria Laura Pelegrina-Lopez, Alicia Ruiz Escobar, Elena, Sáez-Ruiz, Beatriz, Vazquez-Rivero, Antonio, Lara, Belén Vielva Del Campo, Fernando Alcaide Matas, Simbad, Costas-Ochoa, José María García Pérez, Elizabeth, Marmol, Paula Troncoso Pereira, Maria Del Pilar Concejo Cutoli, Juan Ramón Gómez López, Juan Carlos Martín Del Olmo, Paloma Guillamot Ruano, Javier Páramo Zunzunegui, Antonio Albarracín Marín Blázquez, Alfonso, Aliaga-Sanchez, Marta María Arroyo Domingo, Miriam Artés Artés, Ana Isabel Avellaneda Camarena, Aida, Blaya, Emny Rochell Bobadilla Romero, Pedro Vicente Fernández-Fernández, Lorena Galindo Iñiguez, Víctor Javier García Porcel, Clara Giménez Francés, Antonio Javier Gomez Poveda, Rebeca Gonzalez Celdran, Francisco Miguel González Valverde, Laura Guillamon Vivancos, Elena, Gurrea-Almela, Alejandra Jara Maquilón, Jose David Jimenez Parra, Abd Al Aziz Lanagrán Torres, Raquel Lax Perez, Carmen Maria Lopez Lopez, Francisco, Machado, Alfonso Marco Garrido, Florencio Manuel Marin Martinez, Victoria Martínez Muñoz, Esther, Medina, Olimpia, Molina, José Manuel Muñoz Camarena, Julian, Onate, Pedro Antonio Parra Baños, Emilio Peña Ros, Enrique, Rubio, Marina Sánchez Robles, Carlos Sanchez Rodriguez, María Valero Soriano, María Teresa Yepes García, Felipe, Alconchel, Andrés Balaguer Román, Valentín, Cayuela, Ana, Conesa, Ana Delegido García, Pedro José Gil Vázquez, Paula Gómez Valles, Francisco, Gómez-Bosch, Vicente, J León-Muñoz, Francisco, Martínez, Alvaro, Navarro-Barrios, Tatiana, Nicolás-López, Pablo Ramirez Romero, Emiliano, Cano-Trigueros, María Concepcion Alonso González, Leticia Gómez Viana, Ana Pastor Zapata, Elisa Contreras Saiz, Tamara Díaz Vico, Maria, Fernandez-Hevia, Luis Joaquín García Flórez, Raquel, Rodríguez-Uria, Sandra, Sanz, Lorena, Solar-Garcia, Aida Suárez Sánchez, Jaume, Gelonch, Dietmar, Reinaldo, Miriam Abdulkarim Polo, Asier, Aguirre, Marta Alomar Bofill, Santiago, Baena, Ashish, Bartakke, Carmen Cabeza Oliver, Marta Castro Suárez, José Andrés Cifuentes Rodenas, Olga Claramonte Bellmunt, Ant Onia Crespí Mir, Anabel De La Llave Serralvo, Mar, Escales, Isabel Rosa Fernández Burgos, Pablo Gandia Gonzalez, Juan Lliteras Jorge, María Cristina Martínez Canto, Javier, Mata, Andreu, Morell, Naila, Pagès, Sara Pérez Palao, Cristian Plaza Valiente, Catalina Ramon Barcelo, Carmen Reyero Fernández, Albert Reyes Claret, Leticia Rodriguez Vaquero, Maialen Saez de Vicuña Salinas, Pilar Santos Cidon, Concepcion, Segura, Aina, Serra, Maria Serra Guivernau, Maria Soler Pedrola, Marta, Tasende, Marta Torrent Lluch, María Inmaculada Valldeperas Hernández, Rosa-Maria, Yañez-Lpez, Andrea, Craus-Miguel, Laura Fernández Vega, Natalia Pujol Cano, Juan José Segura-Sampedro, Laura Colet Oliver, Ivan Dot Pascuet, Mireia, Duart, Isabel Tello Galindo, Eduardo Arrea Salto, Jaume Cámara Cabrera, Marta Camats Terré, Juan Gabriel Castro Ríos, Marta de la Rosa-Estadella, Anna, Fernandez-Colorado, Anna, Gasulla-Rodriguez, Antonio, Gimenez-Gaibar, Elena, Gonzalez, Yeray Maldonado Sotoca, Matilde, Molina-Corbacho, Montserrat Monfort Mira, Josep, Rodoreda, Marta Santos Espí, Arnau Verdaguer Figuerola, Elisa Angela Diego-Alonso, Jaime, López-Sánchez, Luis, Muñoz-Bellvis, Jacobo, Trebol, Borja, Aguinagalde, Cristina Gabriela Alzate Arsuaga, Ainhoa Andres Imaz, Iñigo, Arana, Coro Aranzabal Urrutia, Mikel, Armendariz, Lorena, Arrabal, Iñigo, Augusto, Adolfo, Beguiristain, Laura, Busto, Ainhoa, Cuevas, Itziar De Ariño, Alejandro, Elúa, Leticia, Fernandez, Arantza, Fernandez-Monge, Lander, Gallego, Alba, Garcia, Amaia Garcia Dominguez, Gregorio, Garmendia, Carmen, Grañén, Pelayo Hevia Rodríguez, Maria, Iraola, José Miguel Izquierdo, Aintzane, Lizarazu, Jon Ander Lizarbe, Claudia Cristina Lopes Moreira, Iker, López, Ruth Marquina González, Tania, Pastor, Adrián Recio Ayesa, Ana Paula Riverola Aso, Carballo, Rodríguez, Araceli, Rodrìguez, Maria Inmaculada Ruiz Montesinos, Patricia, Torres, Jose, Undabeitia, Ainara, Villafruela, Maria Barrionuevo Ramos, David, Blanco, Marta, Calderón, Eva Corral Rubio, Angel, Cuadrado-García, Daniela, Cubek, Ignacio, Fariña, Maria Fernandez LLorente, Natalia Flores Amador, Mariana García Virosta, Luis Garcia-Sancho Tellez, Adelina Gonzalez Martinez, María, Hernandez, Rubén Herreros Ruiz-Valdepeñas, Carmen Jimenez Sanchez, Eduardo Llamazares Cobo, María, López, Javier, López-Martin, Teresa Martínez Marivela, Luis Miguel Martinez Parra, Paloma Maté Mate, Paloma, Medrano, Manuel Moriche Carretero, Sara Núñez O'Sullivan, Manuel Ortega Oria de Rueda, María Begoña Pastor Nieto, Clara, Pérez, Antonio, L Picardo, Remedios Revilla Amores, Carmen Rodríguez Haro, Jose Alberto Rojo López, Fatima Sanchez Cabezudo Noguera, Cristina, Sanz, Daniel Serralta de Colsa, Cristina Valor Garcia, Marta Velasco Martinez, Iván Andújar Lara, Aranzazu, Calero-Lillo, Enrique, López-Ruiz, Alberto Díaz García, Alejandro Menéndez Moreno, Luis Eduardo Pérez-Sánchez, Ángela, Pascual, Miguel Adeba García, Marta Alonso Fernández, Javier Alvarez Gama, Roberto, Ballestero, Loreto Berjon De La Vega, Paola Calleja Hermosa, Mariana, Carrillo-Rivas, Alfonso, Casado, Andrea, Cerveró, Bonifacio Cimadevilla Calvo, Patricia Corriols Noval, Paloma de la Dehesa Cueto-Felgueroso, Miren Jasone Diez Zapirain, José Estevez Tesouro, José Antonio Fernández-Dívar Sánchez, Lucia Garcia Alcalde, Juan García Cardo, Tito García Moreno, Daniel, García-López, Belen Garcia-Montesinos Perea, Miren Gonzalez Benito, Rocio, Gonzalez-Aguado, Miguel Ángel Gordo Vega Gordo-Vega, Jose, Gutierrez-Banos, Jaime Jimeno Fraile, Yolanda Jubete Castañeda, Patricia Lopez Gomez, Antonia Jesús López López, David Mato Mañas, Carmelo, Morales-Angulo, Dieter, Morales-Garcia, Sara, Naranjo, Jose Luis Rabago, Jose Manuel Rabanal, Rocio Revuelta Zorrilla, Adriana Reyes Echeverría, Juan Carlos Rodríguez-Sanjuán, Juan Ramón Sanz, Isabel Simal Badiola, Guillermo, Tejón, Enrique Toledo Martínez, Raquel Varea Malo, Begoña, Fadrique, Tania, Funes, Elena González Revilla, Isaias, Alarcón, Daniel Aparicio Sánchez, Pablo Beltran Miranda, Carmen, Cepeda-Franco, María Josefa Cuevas López, Sandra, Dios-Barbeito, Virginia María Durán Muñoz-Cruzado, Carlos Gonzalez De Pedro, Rosa, M Jimenez-Rodriguez, Francisco, Manresa-Manresa, Gabriel, Marin, Cristobalina, Martin-Garcia, Sara, Martínez-Núñez, Juan Manuel Martos Martinez, Lucas, Mengíbar, Felipe Pareja Ciuro, Eduardo Perea Del Pozo, Veronica Pino Diaz, José, Pintor-Tortolero, Claudia, Quintero-Pérez, Maria Luisa Reyes Diaz, Mercedes Rubio Manzanares Dorado, Alejandro Sanchez Arteaga, Ana, Senent-Boza, Luis, Tallon-Aguilar, Jose, Tinoco-Gonzalez, Luis-Cristobal, Capitan-Morales, Juan Cintas Catena, Javier, Valdes-Hernandez, María Del Campo Lavilla, Alina López De Fernández, Miriam Abellan Lucas, Alba Diaz Padillo, Maria Gómez Romero, Linda Grace Puerto Tamayo, El Mostafa El Yaqine Er Raoudi, Melody García Domínguez, María Ángeles Gascón Domínguez, Marta González Pérez, Alba Hernáez Arzoz, Joana San Anton, Cristian, Ruminot, Hander Guillermo Acosta Diaz, Daniella, Laguado, Kristina, Aghababyan, Alba, Jr, Enrique, Artigues, Rocío, Belda, Miguel, Beltran, Jose Ignacio Blanes, Elena Campos Carot, Miriam, Cantos, Laura, Costa, Carolina Ferrer Gomez, José María Gallego Sánchez, Oscar, Gil-Albarova, Juan, Gilabert-Estellés, Emilio Lopez Alcina, Isabel López Sánchez, Severiano Marin Bertolin, Carolina, Martinez-Perez, Antonio Melero Abellán, Claudia Mulas Fernández, Beatriz, Novoa, Ruth, Nuñez, Pablo Renovell Ferrer, Guijarro-Jorge, Ricardo, Carolina Soledad Romero Garcia, Miguel Sanfeliu Giner, Silvia, M West, Enrique, Zapater, Ignacio, Miranda, Ana, Monís, Alejandro Roselló Añón, María José Sangüesa, Jorge Sanz Romera, Marcos, Adrianzén, Maria Barrios Carvajal, Mireia, Bauzá, Ana Benítez Riesco, Jose Antonio Carbonell Lopez, María-Carmen, Fernández-Moreno, Ricardo Gadea Mateo, Francisco, Garcia, Maris Luisa García-Pérez, Luisa Paola Garzon, Ana, Izquierdo, Maria Lapeña Rodríguez, Carlos, León-Espinoza, Fernando, Lopez, Rosa Martí Fernández, Sara Martínez Castro, Berta Monleón López, Isabel Mora Oliver, David, Moro-Valdezate, Ernesto Muñoz Sornosa, Sara Palomares Casasús, Leticia Pérez Santiago, Mara Albert Fort, Reyes, Balanzá, Lorena Bermell Marco, Carla Carratalá Pérez, Claudia Pilar Clemente Tomas, Marta, Córcoles, Jose Ángel Diez Ares, Carlos Domingo Del Pozo, Nuria Estellés Vidagany, Gonzalo, Garrigos, Mar Gimeno Gimeno Vicente, Blanca Alastrue Giner, Segundo, Gomez-Abril, Paloma, Gonzalez, Paula Gonzálvez Guardiola, Guillermo Sebastian Martínez Fernández, Charo Martínez García, Lucía, Martínez-Costa, Luz María Moratalla Charcos, Sergio Navarro Martínez, Carmen, Payá-Llorente, Álvaro Pérez Rubio, Nuria, Peris, Eduardo Picazo Pineda, Jordi Planelles Gómez, Francisco Ripoll Vidal, Andrea, Roca, Enrique, Salmerón-González, Raquel Segura Roselló, Ramon Trullenque Juan, Cristina Verdejo Gimeno, Jose Miguel Zaragozá García, Gema Zomeño Bravo, Marcos Bruna Esteban, Hanna, Cholewa, Milton de Jesus, Matteo, Frasson, Luis Oliver García, Héctor, J Aguado, Antonio Jose Alonso Villalba, Francisco, Ardura, Carmen Elena Badillo Bercebal, María Bedate Núnez, Alvarez-Ramos Begoña Aranzazu, Juan Beltrán de Heredia, Hugo, Bermejo, Juan Berrocal Cuadrado, Maria Bragado González, Juan, Bustamante-Munguira, Raul Calvo Gonzalez, Yolanda, Carrascal, Ana Belén Casas Marcos, María Carmen Cervera, Sergio Chávez Valladares, Ángel Cilleruelo Ramos, Susana, Cortes, Jesús, Crespo-Sanjuán, María, Cuaresma, Luis Antonio Cuellar Martin, Carlos Ferreras García, Alvaro, Fuentes-Martín, Abel, Ganso, Elena García García, Luis, Garcia-Florez, Virginia, Garcia-Virto, Juan, Gatón, Julio Alberto Gobernado Tejedor, Tania Gómez Sanz, Jose Ignacio González Martín, María Begoña Gregorio Crespo, Ana Herranz Arriero, Jose, Herreros, Marta Ibáñez Nieto, César, Infante, Carlos, Jezieniecki, Moises, Juarez, Gregorio de Jesus Labrador Hernandez, Ana Patricia Legido Morán, Ricardo León Fernández, Alejandro, Leon-Andrino, Almudena, Llorente, Maria Lopez Pais, Mauricio Loucel Bellino, Sergio, Martin, Miguel Angel Martin-Ferrero, Gonzalo Martinez Municio, Elvira Mateos Alvarez, José María Matilla, Luis María Merino Peñacoba, Mario, Montes-Manrique, Fernando Natal Álvarez, David, C Noriega, Henar Nuñez Del Barrio, Francisco Javier Ortiz de Solórzano Aurusa, Lucía, Pañeda, Victoria Pascual Escudero, Miguel Pascual Samaniego, Adela, Pereda, Marta Pérez Febles, Laura, Pesquera, Maria, Plata, Emma Puertas Ruiz, Mario, Rodriguez-Lopez, Alejandro Romero de Diego, Ana, Ruano, María Ruiz Soriano, Cristina Sánchez Torralvo, Silvia Santiago Maniega, Bárbara, Segura-Méndez, Clarisa Simon Perez, José, Soro-García, Paula Suárez Mansilla Suárez-Mansilla, Jeancarlos Trujillo Díaz, Mª Esther Valsero Herguedas, Andrea Vazquez Fernandez, Eduardo Velasco García, Ana, Zabalza, Álvaro Zamora Horcajada, Fernando Acebes García, Enrique Asensio Díaz, Martín, Bailón, Alejandro David Bueno Cañones, Alvaro Centeno Velasco, Ekta Choolani Bhojwani, Fernando Labarga Rodríguez, Sara, Mambrilla, Pablo, Marcos-Santos, Toledano, Miguel, David Pacheco Sánchez, Baltasar, Pérez-Saborido, Pilar, Pinto, Katherine, Plua, Javier Sanchez Gonzalez, Vicente, Simo, Rosalía Velasco López, Sandra Veleda Belanche, Fabiola Eugenia Michel Campos, Iciar Muñoz Lindez, Maria, Balluerca, Maite, Camuera, Pablo, Helguera, Imanol, Herrero, Patricia Paunero Vazquez, María, Sánchez-Rubio, Isami, Soeda, María Dolores Arribas Del Amo, Vicente Manuel Borrego Estella, Estefania, Casas, Néstor Castán Villanueva, Daniel Delfau Lafuente, Elena Delgado Blanco, María, Domingo, Ismael Gil Romea, Azucena, Gonzalo, Emilio Lagunas Lostao, Noelia Lete Aguirre, Yaiza Martinez Lahoz, Jesús Víctor Pérez-Tierra Ruiz, Maria Del Mar Soriano, Isabel Valero Lázaro, Esmeralda Carnicer Escusol, Guillermo Pola Bandres, Juan Luis Blas Laina, Beatriz, Cros, Patricio Andrés Freile Pazmiño, David, Garcia-Aguilera, Ana Mejía Casado, Ana, Nogués, Issa Talal El-Abur, Carlos, Yánez, Isabel Gascon Ferrer, Carlos, Gracia-Roche, Ursula María Jariod Ferrer, María Victoria Simón Sanz, Tomas, Uson, Waseem, Ahamed, Sumudu, Jayasinghe, Eranda, Karunadasa, Prathibha, Nelihela, Sujeewa Priyantha Bandara Thalgaspitiya, Dickson, Wickramarathna, Nagenthiram, Harivallavan, Pirashanthan, Nagarasa, Eranga, Perera, Kanapathipillai, Piratheep, Vithranage Srimantha Dewsiri Rodrigo, Meera, Thayalan, Rajendram, Thayaparren, Arulprashanth, Arulanantham, Kanishka De Silva, Gagana, Ganga, Anuja Nadeeshan Kumarasinghe, Mahanada, Udukala, Koculen, Vimaleswaran, Prashanthan, Yogarajah, Ravindri, Jayasinghe, Probhodana, Ranaweera, Mohamed, Rishard, Dharmabandhu, N Samarasekera, Sanjeewa, Seneviratne, Sivasuriya, Sivaganesh, Chamal, Fernando, Nishantha, Mendis, Balasingam, Balagobi, Balasupramaniam, Sathesan, Lanka, Dasanayake, Malitha, Patabendige, Wickramasooriya, Dj, Kugarajh, Ganeshapillai, Sathyamoorthy, Prasanna, Dileepa, Ediriweera, Sumudu, Kumarage, Asanka, Jayawardane, Athula, Kaluarachchi, Pituwala Liyanage Adithya Sirisena, Abubakr, Abubakr, Hozifa, Mohamed, Ismail, Mustafa, Mogahid, Sharfeldein, Samir, Ismail, Reem, Musa, Monira, Sarih, Mussab, Abaker, Eman Adam Abdalla, Mohamad, Abdelbagi, Alsafe, Adlan, Ahmed, Alnaeem, Safa, Atyah, Yasir, Awad, Rsheeda, Dawelbait, Mohamed El Hag, Ibrahim, Elbashir, Sami, Eldirdiri, Samwal, Eldirdiri, Mohammed Eltahier Abdalla Omer, Lana Abdalgadir Ahmed Mohamed, Hiba Hassan Rehmtallah Ahmed, Mohammed Balla Yousif Balla, Abdulmoiz, Aljafari, Abdulmalek, Aljafari, Elsagad, Mohamed, Abdulkader, Mohammad, Abdulkader, Shaar, Mohamed Nafea Shaar, Maab Hussein Yousif Elhafiz, Mohammed Husien Yosif Elhafiz, Abubakr Ali Mohammed Alhassan Humidan, Almigdad, Ali, Hisham, Eljack, Mohamedyasin, Elrashid, Manhal, Ahmed, Albrra, Alhag, Douaa, Ali, Mohammed Ahmed Babikir, Imad, Bakheit, Hytham K, S Hamid, Sami, Mohamed, Walid, Shaban, Nidhal, Siddig, Mohamed, Suliman, Rihab Yasir Abdelmagid, Abubaker, Yassin, Omer, Abbas, Eltahir, Abdelrahim, Muhammed, Ahmed, Mohamed, Elobaid, Adil, Hashim, Ali, Mohamed, Omer, Mohamed, Khalid, Osman, Abdallah, Yousif, Safaa, Abdulaal, Marwa, Elsadig, Mohammed, Hussain, Malaz Amir Ataalmanan, Doha Amir AtaAlmanan, Tebyan Amir AtaAlmanan, Alaa, Elgaili, Maria, Mohamed, Usra, Omara, Alkhansa, Osman, Amna, Osman, Safaa, Saad, Abdelkareem, Ahmed, Ali Adil Ali Karar, Aya, Alhassan, Mohanad, Alsidig, Mohamed, Eljack, Mohammed Ibrahim Mohammed Ali, Awad Kamal Awad Osman, Liena, Mohamed, Samah Ibrahim Omer Mohamed Osman Mohamed Osman, Altayeb, Mohammed, Ayman, Mohammed, Khadija, Muhmmed, Eltahir, Musa, Egbal Sahal Abdelmajed, Khalid Z M, Y Hamid, Omnia M, M Yousif, Mahmoud, Saleh, Osman, Bashir, Yassein, Elhussein, Omar, Madani, Eva, Angenete, Jennifer, Park, Lars, Gillberg, Monir, Jawad, Linas, Pieteris, Yousif, Saeed, Sergej, Safonov, Martin, Spångfors, Henrik, Andersson, Hans, Bahlmann, Karin Björnström Karlsson, Michelle, Chew, Lara, Daham, Lina De Geer, Helen, Didriksson, Gunilla, Gagnö, Carina, Jonsson, Anna, Oscarsson, Pamela, Buchwald, Mathilde, Delorme, Marie-Louise, Lydrup, Shahin, Mohseni, Arvid, Pourlotfi, Souheil, Reda, Kajsa, Anderin, Nina, Blomme, Josefin, Segelman, Malin, Simlund, Anders, Thorell, Fredrik, Wogensen, Daniel, Danielsson, Peter, Elbe, Rebecka, Hultgren, Boel, Hynning, Fredrik, Klevebro, Karin, Lind, Ebba, K Lindqvist, Carl, Montan, Ernesto, Sparrelid, Clara Svenberg Lind, Jeremy, Wales, Andreas, Älgå, Martin, Nordberg, Emil, Pieniowski, Ioannis, Gkekas, Niklas, Löfgren, Karolina, Niska, Robert, Zürner, Silvio, Däster, Otto, Kollmar, Savas, Soysal, Stephanie, Taha-Mehlitz, Athanasios, Tampakis, Dominik Valentin Flury, Marie, Heyne-Pietschmann, Gregor Jan Kocher, Ana, M Calinescu, Barbara, Wildhaber, Markus, Gass, Jürg, Metzger, Andreas, Scheiwiller, Lukas, Briner, Oliver, Dwidar, Steven, Grandjean, Pietro, Ricciardi, Alexandra, Calmels, Christodoulou, Michel, Morena, Antonilli, Dimitrios, Christoforidis, Alessandra, Cristaudi, Jacopo, Galafassi, Maria Luisa Gasparri, Francesco, Mongelli, Martino, Munini, Andrea, Papadia, Sotirios Georgios Popeskou, Alex, Alfieri, Thomas, Bächler, Matteo, Giardini, Christian, Gingert, Laura, Guglielmetti, Inna, Meyer, Tobias, Müller, Daniel, Schöni, Folco, Solimene, Frank, Weidner, Marco, Bueter, Daniel, Gero, Amelie, Müller, Carmen, Portenkirchner, Andreas, Thalheimer, Jeannette, Widmer, Ahmad, Hmaideh, Alaa, Kour, Saleem, Swaes, Omar, Alannaz, Ramez, Aljasem, Ezeddin, Dabbagh, M Wafa Hamoud Alhussein, Amr, Hamza, Mazen, Mohammad, Abd El-Fattah Mouhandes, Mohamad, Shareeda, Mohammad Nour Shashaa, Mousa, Sifat, Sheraa, Tahhan, Rahaf, Toutounji, Mohamed, Abdulrahman, Albaraa, Abdulsalam, Ziad Al Jarad, Hala, Alayyoubi, Dina, Alfarra, Ahmad, Alhamid, Mahmoud, Alnasser, Mulham, Gharib, Ruwaid, Gharib, Obaida, Kabel, Osama, Kherallah, Abdulqader, Klaho, Mohamed Shukri Najjar, Ahmad, Razouk, Joud, Shiekhoni, Wael, Alkhaleel, Amira, Almosa, Mohammad, Aloulou, Maen, Alzaeem, Khaled, Arnaout, Muhamad Zakaria Brimo Alsaman, Mohamad, Estanbouli, Hanadi, Hawa, Ahmad Nbrass Kabawi, Ghina, Maarawi, Yehia, Mashhadany, Sana Shaikh Torab, Waleed, Abd, Tayma Abd Alghafour, Hani, Abdalnour, Nazeeh Al Aktaa, Marwan Al Aliwy, M Maher Al Arje, Tasneem Al Najjar, Ahmad, Al-Mouakeh, Ahmad, Aldakhil, Aos, Alhamid, Hasan, Alhasan, Mohamad Shadi Alkarrash, Jumaa, Alkhamis, Sara, Alshekh, Ahmad Yamen Arnaout, Oula, Azizeh, Mohammed, Dalaleh, Aghyad, Danial, Zain, Douba, Raghad, Ghadri, Mohammad Maen Ghannam, Anas, Ghawi, Luma Haj Kassem, M Yasser Halwani, Shahed, Hamadieh, Mohammad, Hanino, Ala Aldeen Hasan, Haya, Jawish, Nasr Ullah Kabbani, Saadullah, Kabbany, Mohamad, Kadi, Lama, Kadoura, Ahmad Amir Kayali, Ammar, Kayyali, Aya, Kelzia, Amana, Kezze, Abdullah, Khalaf, Maymona, Khayata, Mohammad Nour Kitaz, Mohammad, Kour, Raghad, Makki, Ruqaya, Masri, Joseph, Masri, Noor, Masri, Muhammad, Mazketly, Shiar, Mustafa, Ezzeldin, Nashed, Yaman Qoudra Danial, Hasan, Raslan, Rima, Salem, Mohammed Asaad Salem, Thabet Sayed Bakir, Manaf, Sharabaji, Majd Sheikh Alganameh, Duaa Sheikh Kadro, Joudy, Shurbatji, Mohammad Noor Sultan, Dana, Sultan, Hala, Swied, Bakri Tarras Jarkas, Tayf, Toutounji, Fadi, Ward, Rama, Zazo, Aya, Zazo, Zainab, Zeino, Mohamed, Alaktaa, Wael, Alsado, Hala, Fares, Nouran, Hawa, Hamza, Ibrahim, Abdulmonem, Kawas, Mourad, Niazi, Bayan, Toutounji, Mohammad, Abdow, Mohamad, Ahmad, Tareq, Ahmad, Rawan Al Azhar, Hiba Al Hage Diab, Rahaf Al Mulke, Mohammad, Al-Jadaan, Ahmad, Alhussein, Zahra, Alnajem, Omar, Alneser, Bayan, Alsaid, Elias, Azar, Lubna, Bakr, Ammar, Hamza, Yara, Houdifa, Sami, Jomaa, Samer, Kefo, Hiba, Mardini, Alaa, Mohammad, Fadi, Rayya, Fatima, Razzouk, Mohannad, Saleh, Anwar, Shamandi, Ammar Youzkatli Alkhatib, Omar Abdul Salam, Dany, Ajami, Mohammad, Alhamid, Ahmad, Alkhaledi, Danny, Hadidi, Massa, Jabra, Mamdouh, Kallas, Antoine, Laktine, Joelle, Naem, Naya, Naoum, Ghena Mohammed Fawaz Ashour, Ahmad, Alhouri, Deema, Fallouh, Ahmad, N Mohammad, Ahmad, Rmman, Ali, Slitin, Christine, Tanos, Ibrahim, Wakim, Hanaa, Zahrawi, Majd, Abouassi, Layth, Abouassi, Ayham, Aboutrab, Basel, Ahmad, Ahmad Mustafa Ahmad, Aya, Ahmad, Afaf, Ahmad, Mohamad, Alabras, Mohammad, Albasheer, Ola, Alkasser, Mhd Khaled Alkasser, Ali, Alkhdor, Marah, Azkoul, Mohammad Karam Chaaban, Haya, Deeb, Basel, Jazieh, Basel, Kouz, Youssef, Kozah, Raied, Mohamad, Ammar, Mohammad, Mhd Zied Nasri, Mohammed Mouaz Shebani, Mohammed, Shwin, Alaa, Sommaq, Amal, Youssef, Tala Al Asadi, Suhad, Alkhateb, Rasha Khalil Alsayyad, Roula, Altom, Mhd Amin Alzabibi, Batoul, Bakkar, Hlma, Ismail, Salma Khadem Alsrouji, Sara, Melhem, Mohamad, Sankari, Mosa, Shibani, Noura, Shujaa, Ibrahim, 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Giuseppe Salamone, Francesca Toia, Massimiliano Tripoli, Nepogodiev, D, Rosati, R, Surgery, Medicine and Pharmacy academic/administration, Basic (bio-) Medical Sciences, Surgical clinical sciences, Faculty of Medicine and Pharmacy, Gastroenterology, Medical Oncology, Clinical sciences, Breda, João, ARD - Amsterdam Reproduction and Development, Paediatric Surgery, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, AGEM - Endocrinology, metabolism and nutrition, Graduate School, Tytgat Institute for Liver and Intestinal Research, Laura Alberici, Filippo Antonacci, Alessandro Arena, Angela Belvedere, Fabio Bernagozzi, Paolo Bernante, Pietro Bertoglio, Lorenzo Bianchi, Maria Bisulli, Barbara Bonfanti, Safia Boussedra, Jury Brandolini, Crescenzo Cacciapuoti, Stefano Cardelli, Riccardo Casadei, Matteo Cescon, Alessandro Cipolli, Riccardo Cipriani, Alfredo Conti, Luca Contu, Francesco Costa, Niccolo’ Daddi, Eugenia De Crescenzo, Pierandrea De Iaco, Alessandra De Palma, Massimo Del Gaudio, Anna Nunzia Della Gatta, Giampiero Dolci, Giulia Dondi, Matteo Droghetti, Sergio Nicola Forti Parri, Elena Garelli, Chiara Gelati, Giuliana Germinario, Federico A. Giorgini, Carlo Ingaldi, Elio Jovine, Kenji Kawamukai, Antonio Lanci Lanci, Raffaele Lombardi, Maria Elisa Lozano Miralles, Claudio Marchetti, Michele Masetti, Francesco Minni, Daniele Morezzi, Daniele Parlanti, Alice Pellegrini, Anna Myriam Perrone, Anna paola Pezzuto, Marco Pignatti, Gianluigi Pilu, Valentina Pinto, Gilberto Poggioli, Silvana Bernadetta Puglisi, Diego Raimondo, Matteo Ravaioli, Claudio Ricci, Sara Ricciardi, Francesco Ricotta, Roberta Rizzo, Angela Romano, Matteo Rottoli, Riccardo Schiavina, Renato Seracchioli, Matteo Serenari, Margherita Serra, Piergiorgio Solli, Gioia Sorbi, Mario Taffurelli, Marta Tanzanu, Achille Tarsitano, Marco Tesei, Gabriele Vago, Tommaso Violante, Simone Zanotti, Tommaso Frisoni, leonardo solaini, giorgio ercolani, Fruscio, R, Ornaghi, S, Collaborative, Covidsurg, Collaborative, Globalsurg, Palmisano, Silvia, de Manzini, Nicolo', Žundienė, Laura, Dulskas, Audrius, Kuliavas, Justas, Čekauskas, Albertas, Kielaitė-Gulla, Aistė, Poškus, Tomas, Strupas, Kęstutis, Želvys, Arūnas, COVIDSurg Collaborative, GlobalSurg Collaborative, Department of Surgery, HUS Abdominal Center, Simoes, Jff, Li, E, Picciochi, M, Glasbey, Jc, Baiocchi, G, Blanco-Colino, R, Chaudhry, D, Alameer, E, El-Boghdadly, K, Wuraola, F, Ghosh, D, Gujjuri, Rr, Harrison, Em, Lule, H, Kaafarani, H, Khosravi, M, Kronberger, I, Leventoglu, S, Mann, H, Mclean, Ka, Mengistu, Gm, Modolo, Mm, Ntirenganya, F, Norman, L, Outani, O, Pius, R, Pockney, P, Qureshi, Au, Roslani, Ac, Satoi, S, Shaw, C, Bhangu, A, Omar, Om, Ahmed, Wur, Argus, L, Ball, A, Bywater, Ep, Brar, A, Dawson, Be, Duran, I, Elhadi, M, Jones, C, Kamarajah, Sk, Keatley, Jm, Lawday, S, Marson, Ej, Ots, R, Santos, I, Taylor, Eh, Trout, Im, Varghese, C, Venn, Ml, Xu, W, Dajti, I, Gjata, A, Kacimi, Seo, Boccalatte, L, Cox, D, Townend, P, Aigner, F, Kronberger, Ie, Samadov, E, Alderazi, A, Hossain, K, Padmore, G, van Ramshorst, G, Lawani, I, Cerovac, A, Delibegovic, S, Gomes, Gma, Buarque, Il, Gohar, M, Slavchev, M, Nwegbu, C, Agarwal, A, Martin, J, Ng-Kamstra, J, Olivos, M, Lou, Wh, Ren, Dl, Calvache, Ja, Rivera, Cjp, Hadzibegovic, Ad, Kopjar, T, Mihanovic, J, Jimenez, Pma, Gouvas, N, Klat, J, Novysedlak, R, Amisi, N, Christensen, P, El-Hussuna, A, Batista, S, Lincango-Naranjo, E, Emile, S, Sandoval, Daa, Dhufera, H, Hailu, S, Mengesha, Mg, Kauppila, Jh, Arnaud, Ap, Demetrashvili, Z, Albertsmeier, M, Lederhuber, H, Loffler, Mw, Acquah, Dk, Ofori, B, Tabiri, S, Metallidis, S, Tsoulfas, G, Aguilera-Arevalo, Ml, Recinos, G, Mersich, T, Wettstein, D, Kembuan, G, Milan, Pb, Khosravi, Mh, Mozafari, M, Hilmi, A, Mohan, H, Zmora, O, Gallo, G, Pata, F, Pellino, G, Fujimoto, Y, Kuroda, N, Abou Chaar, Mk, Ayasra, F, Fakhradiyev, I, Hamdun, Ih, Jin-Young, J, Jamal, M, Karout, L, Gulla, A, Rasoaherinomenjanahary, F, Samison, Lh, Sanchez, Iid, Gonzalez, D, Martinez, L, Martinez, Mj, Nayen, A, and Ramos-De la Medina, A
Subjects: Male, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], MULTICENTER, infectious diseases, 0302 clinical medicine, 030202 anesthesiology, Anesthesiology, Cirugía, 80 and over, Prospective Studies, Young adult, Child, Lung, Aged, 80 and over, COVID-19, delay, SARS-CoV-2, surgery, timing, SARS‐CoV‐2 infection, Operative, Child, Preschool, Pneumonia & Influenza, Infection, Cohort study, Human, medicine.medical_specialty, Clinical Sciences, Sars-cov-2, GlobalSurg Collaborative, Settore MED/28 - MALATTIE ODONTOSTOMATOLOGICHE, 03 medical and health sciences, Clinical Research, Biodefense, Correspondence, Humans, PULMONARY COMPLICATIONS, CRIANÇAS EM IDADE PRÉ-ESCOLAR, Aged, Science & Technology, Cirurgia, Prevention, Infant, Odds ratio, Pneumonia, Prospective Studie, Clinical research, Surgery, Human medicine, 610 Medizin und Gesundheit, 1109 Neurosciences, Internationality, Settore MED/29 - CHIRURGIA MAXILLOFACCIALE, Settore MED/18 - CHIRURGIA GENERALE, Adolescent, Adult, Cohort Studies, Female, Middle Aged, Surgical Procedures, Operative, Time, Young Adult, Practice Guidelines as Topic, gastroenterology, Medicine and Health Sciences, 030212 general & internal medicine, Prospective cohort study, Mortality rate, Covid19, Infectious Diseases, Patient Safety, medicine.symptom, 6.4 Surgery, Life Sciences & Biomedicine, 610 Medicine & health, COVID-19, SARS-CoV-2, delay, surgery, timing, Asymptomatic, NO, COVIDSurg Collaborative, Vaccine Related, All institutes and research themes of the Radboud University Medical Center, medicine, Mortalitat, ddc:610, Mortality, Preschool, LS7_4, Surgical Procedures, business.industry, Neurosciences, Evaluation of treatments and therapeutic interventions, 1103 Clinical Sciences, 3126 Surgery, anesthesiology, intensive care, radiology, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Anesthesiology and Pain Medicine, Emerging Infectious Diseases, Good Health and Well Being, Mortalidad, Cohort Studie, business
Abstract: Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay. ispartof: ANAESTHESIA vol:76 issue:6 pages:748-758 ispartof: location:England status: published
Published: 2021
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24. Molecular characterization of vulvar squamous cell cancer: High time to gain ground

Author: Alain G. Zeimet
Subjects: Squamous cell cancer, Oncology, Vulvar Neoplasms, business.industry, Cancer research, MEDLINE, Carcinoma, Squamous Cell, Obstetrics and Gynecology, Medicine, Humans, Female, business
Published: 2020

25. Clinical impact of EZH2 and its antagonist SMARCA4 in ovarian cancer

Author: I Tsibulak, Christian Marth, K Leitner, Heidi Fiegl, Daniel Reimer, K Knoll, Verena Wieser, and Alain G. Zeimet
Subjects: Oncology, Adult, medicine.medical_specialty, Percentile, Science, Chromatin remodelling, macromolecular substances, Carcinoma, Ovarian Epithelial, Chromatin remodeling, Article, Ovarian cancer, Internal medicine, Medicine, Humans, Enhancer of Zeste Homolog 2 Protein, RNA, Messenger, Fallopian Tubes, Aged, Neoplasm Staging, Aged, 80 and over, Ovarian Neoplasms, Multidisciplinary, Receiver operating characteristic, business.industry, EZH2, Ovary, Antagonist, DNA Helicases, Nuclear Proteins, Middle Aged, medicine.disease, Survival Analysis, Gene Expression Regulation, Neoplastic, ROC Curve, Concomitant, Case-Control Studies, Mad2 Proteins, SMARCA4, Female, Neoplasm Grading, Poly(ADP-ribose) Polymerases, business, Signal Transduction, Transcription Factors
Abstract: SMARCA4 and EZH2 are two functional key players of their respective antagonizing chromatin remodeling complexes SWI/SNF and PRC2. EZH2 inhibitory drugs may abrogate pro-oncogenic features of PRC2 and turn the balance to cell differentiation via SWI/SNF activity in cancers. SMARCA4 and EZH2 expression was assessed by RT-PCR in 238 epithelial ovarian cancers (OCs) and put in relation to clinico-pathological parameters and patients’ outcome. Optimal thresholds for high and low expression of both variables were calculated by the Youden’s index based on receiver operating characteristic (ROC) curves. High SMARCA4 mRNA expression was independently associated with favorable progression-free survival (PFS) (P = 0.03) and overall survival (OS) (P = 0.018). As Youden’s threshold determination for EZH2 yielded a S-shaped ROC-curve, two cut-off points (29th and 94th percentile) predicting opposite features were defined. Whereas EZH2 mRNA levels beyond the 29th percentile independently predicted poor PFS (P = 0.034), Cox-regression in EZH2 transcripts above the 94th percentile revealed a conversion from unfavorable to favorable PFS and OS (P = 0.009 and P = 0.032, respectively). High SMARCA4 expression associates with improved survival, whereas moderate/high EZH2 expression predicts poor outcome, which converts to favorable survival in ultra-high expressing OCs. This small OC subgroup could be characterized by REV7-abrogated platinum hypersensitivity but concomitant PARP-inhibitor resistance.
Published: 2020

26. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial

Author: Jacobus Pfisterer, Catherine M Shannon, Klaus Baumann, Joern Rau, Philipp Harter, Florence Joly, Jalid Sehouli, Ulrich Canzler, Barbara Schmalfeldt, Andrew P Dean, Alexander Hein, Alain G Zeimet, Lars C Hanker, Thierry Petit, Frederik Marmé, Ahmed El-Balat, Rosalind Glasspool, Nikolaus de Gregorio, Sven Mahner, Tarek M Meniawy, Tjoung-Won Park-Simon, Marie-Ange Mouret-Reynier, Cristina Costan, Werner Meier, Alexander Reinthaller, Jeffrey C Goh, Tifenn L'Haridon, Sally Baron Hay, Stefan Kommoss, Andreas du Bois, Jean-Emmanuel Kurtz, Sven Ackermann, Christoph Anthuber, Mustafa Aydogdu, Angelika Baldauf, Wolfgang Bauer, Dirk Behringer, Antje Belau, Alexandra Bender, Cosima Brucker, Alexander Burges, Trygve Daabach, Dominik Denschlag, Mustafa Deryal, Steffen Dörfel, Juliane Ebert, Tanja Fehm, Susanne Maria Feidicker, Gabriele Feisel-Schwickardi, Ricardo Felberbaum, Matthias Frank, Gerhard Gebauer, Bernd Gerber, Axel Gerhardt, Andrea Grafe, Martin Griesshammer, Eva-Maria Grischke, Isolde Gröll, Martina Gropp-Meier, Dietrich Hager, Volker Hanf, Carla Verena Hannig, Peer Hantschmann, Tanja Hauzenberger, Uwe Herwig, Martin Heubner, Carsten Hielscher, Felix Hilpert, Thomas Hitschold, Manfred Hofmann, Christian Jackisch, Wolfgang Janni, Ludwig Kiesel, Yon-Dschun Ko, Hans-Joachim Koch, Petra Krabisch, Peter Krieger, Thomas Kubin, Thorsten Kühn, Björn Lampe, Peter Ledwon, Sabine Lemster, Benno Lex, Clemens Liebrich, Ralf Lorenz, Hans-Joachim Lück, Peter Mallmann, Wolfgang Meinerz, Götz Menke, Volker Möbus, Thomas Müller, Volker Müller, Tanja Neunhöffer, Angelika Ober, Gülten Oskay-Özcelik, Horst Ostertag, Martin Pölcher, Beate Rautenberg, Daniel Rein, Wilhelm Reiter, Andreas Rempen, Ingo Runnebaum, Marcus Schmidt, Sabine Schnohr, Heinz Scholz, Willibald Schröder, Eike Simon, Antje Sperfeld, Annette Steckkönig, Hans-Georg Strauß, Ronaldo Stuth, Jürgen Terhaag, Falk Thiel, Marc Thill, Oliver Tomé, Christoph Uleer, Susanne Vogel, Hermann Voß, Michael Weigel, Ulrich Winkler, Arthur Wischnik, Tobias Zeiser, Andreas Zorr, Ros Glasspool, Emma Hudson, Rachel Jones, Judith Lafleur, Christian Marth, Edgar Petru, Yoland Antill, Mary Azer, Sally Baron-Hay, Philip Beale, Stephen Begbie, Allison Black, Karen Briscoe, Andrew Dean, Jeffrey Goh, Sandra Harvey, Chee Lee, Marco Matos, Tarek Meniawy, Inger Olesen, Catherine Shannon, Paul Vasey, Sophie Abadie-Lacourtoisie, Olivier Arsene, Sophie Barthier, Célia Becuwe-Roemer, Dominique Berton-Rigaud, Maria Cappiello-Bataller, Stéphanie Catala, Francesco Del Piano, Gaël Deplanque, Raymond Despax, Nadine Dohollou, Claire Garnier-Tixidré, Julien Grenier, Emmanuel Guardiola, Anne-Claire Hardy-Bessard, Claudia Lefeuvre-Plesse, Marianne Leheurteur, Anne Lesoin, Charles-Briac Levache, Raffaele Longo, Alain Lortholary, Jérôme Meunier, Nadia Raban, Olivier Romano, Jean-Michel Vannetzel, Alain Zannetti, Cancers et préventions, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Obstetrics and Gynecology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of OB/Gyn, University Breast Center Franconia, Univeristy Hospital Erlangen, Goethe-Universität Frankfurt am Main, Mines Nantes (Mines Nantes), Division Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, Universität Heidelberg [Heidelberg] = Heidelberg University, Department of Gynecology, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hannover Medical School [Hannover] (MHH), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Medizinische Universität Wien = Medical University of Vienna, Les Hôpitaux Universitaires de Strasbourg (HUS), Department of Gynaecology, Universität Greifswald - University of Greifswald, University Hospital Düsseldorf, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, University of Rostock, Städtische Kliniken, Department of Gynecology and Obstetrics, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Hämatologie/Onkologie, Klinikum Traunstein, Department of OB/Gyn, Hospital Bayreuth, École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Department of Gynecology and Obstetrics, Center for Integrated Oncology, Bonn University Medical Center, University Hospital Bonn, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Chemical Metals Science Department, Max Planck Institute for Chemical Physics of Solids (CPfS), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Leopold Franzens Universität Innsbruck - University of Innsbruck, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Hospitalier de Blois (CHB), CRLCC René Gauducheau, Hôpital Saint-Joseph [Marseille], Polyclinique Bordeaux Nord Aquitaine (PBNA), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Department of Medical Oncology, CRLCC Eugène Marquis (CRLCC), Service d'Oncologie Médicale, CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Polyclinique Francheville, Centre Catherine-de-Sienne [Nantes] (CCS), Centre Hospitalier Régional d'Orléans (CHRO), Hématologie clinique [CH Cholet], CH Cholet, Universität Heidelberg [Heidelberg], Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Tübingen [Germany], HESAM Université (HESAM)-HESAM Université (HESAM), University Hospital of Bonn, University of Innsbruck, Centre Hospitalier de Blois (CH Blois), Polyclinique Bordeaux Nord Aquitaine, Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Lille Nord de France (COMUE)-UNICANCER
Subjects: 0301 basic medicine, genetic structures, endocrine system diseases, [SDV]Life Sciences [q-bio], Gastroenterology, law.invention, Carboplatin, Polyethylene Glycols, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Ovarian Neoplasms, education.field_of_study, Standard treatment, Middle Aged, female genital diseases and pregnancy complications, 3. Good health, Bevacizumab, Oncology, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Austria, Female, France, medicine.drug, Adult, medicine.medical_specialty, Paclitaxel, Population, 03 medical and health sciences, Internal medicine, medicine, Fallopian Tube Neoplasms, Humans, education, Aged, Platinum, business.industry, Australia, eye diseases, Regimen, 030104 developmental biology, chemistry, Doxorubicin, sense organs, Neoplasm Recurrence, Local, business
Abstract: Background:\ud State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin–paclitaxel or carboplatin–gemcitabine) or the most active non-bevacizumab regimen: carboplatin–pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin–pegylated liposomal doxorubicin combined with bevacizumab.\ud Methods:\ud This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK. Eligible patients (aged ≥18 years) had histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with first disease recurrence more than 6 months after first-line platinum-based chemotherapy, and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were stratified by platinum-free interval, residual tumour, previous antiangiogenic therapy, and study group language, and were centrally randomly assigned 1:1 using randomly permuted blocks of size two, four, or six to receive six intravenous cycles of bevacizumab (15 mg/kg, day 1) plus carboplatin (area under the concentration curve [AUC] 4, day 1) plus gemcitabine (1000 mg/m 2, days 1 and 8) every 3 weeks or six cycles of bevacizumab (10 mg/kg, days 1 and 15) plus carboplatin (AUC 5, day 1) plus pegylated liposomal doxorubicin (30 mg/m 2, day 1) every 4 weeks, both followed by maintenance bevacizumab (15 mg/kg every 3 weeks in both groups) until disease progression or unacceptable toxicity. There was no masking in this open-label trial. The primary endpoint was investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy data were analysed in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug. This completed study is registered with ClinicalTrials.gov, NCT01837251.\ud Findings:\ud Between Aug 1, 2013, and July 31, 2015, 682 eligible patients were enrolled, of whom 345 were randomly assigned to receive carboplatin–pegylated liposomal doxorubicin–bevacizumab (experimental group) and 337 were randomly assigned to receive carboplatin–gemcitabine–bevacizumab (standard group). Median follow-up for progression-free survival at data cutoff (July 10, 2018) was 12·4 months (IQR 8·3–21·7) in the experimental group and 11·3 months (8·0–18·4) in the standard group. Median progression-free survival was 13·3 months (95% CI 11·7–14·2) in the experimental group versus 11·6 months (11·0–12·7) in the standard group (hazard ratio 0·81, 95% CI 0·68–0·96; p=0·012). The most common grade 3 or 4 adverse events were hypertension (88 [27%] of 332 patients in the experimental group vs 67 [20%] of 329 patients in the standard group) and neutropenia (40 [12%] vs 73 [22%]). Serious adverse events occurred in 33 (10%) of 332 patients in the experimental group and 28 (9%) of 329 in the standard group. Treatment-related deaths occurred in one patient in the experimental group (
Published: 2020
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27. Wirksamkeit der Ovarialkarzinom-Früherkennung: Eine Simulationsstudie basierend auf Daten aus dem Klinischen Tumorregister der AGO

Author: A G Zeimet, L Steinkasserer, and C Marth
Published: 2020
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28. Joint Guideline of the OEGGG, AGO, AGK and ÖGZ on the Diagnosis and Treatment of Cervical Intraepithelial Neoplasia and Appropriate Procedures When Cytological Specimens Are Unsatisfactory

Author: Petra Kohlberger, Karl Tamussino, Anton Graf, Peter Regitnig, Alexander Reinthaller, Lukas Hefler, Andreas Widschwendter, Wolfgang Pokieser, Thomas Fiedler, Wolfgang Eppel, Christian Marth, Olaf Reich, Georg Braune, Heinz Kölbl, Elmar A. Joura, and Alain G. Zeimet
Subjects: medicine.medical_specialty, zervikale intraepitheliale Neoplasie, Bethesda system, Kolposkopie, Guideline/Leitlinie, cervical intraepithelial neoplasia, Cervical intraepithelial neoplasia, Zytologie, 03 medical and health sciences, 0302 clinical medicine, Maternity and Midwifery, medicine, GebFra Science, Colposcopy, Cervical cancer, Gynecological oncology, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, business.industry, colposcopy, Obstetrics and Gynecology, Guideline, medicine.disease, Private practice, 030220 oncology & carcinogenesis, Family medicine, cytology, business
Abstract: Purpose On January 1st, 2018, the ÖGZ (Austrian Society of Cytology) revised its cytological nomenclature to make it more similar to the 2015 Bethesda system. Following these changes, the Austrian Society of Gynecology and Obstetrics felt it necessary to revise the approach currently used in Austria to diagnose and treat CIN and to review the procedures to be followed when the quality of cytological specimens is unsatisfactory. It was not possible to adopt the German S3 guideline “Prevention of Cervical Cancer” in its entirety, because the Munich III gynecological cytology nomenclature used in Germany is not used in Austria. This made it necessary to compile a separate scientific opinion for Austria. Methodology The OEGGG worked together with the ÖGZ (Austrian Society for Cytology), AGO Austria (Austrian Working Group for Gynecological Oncology), the AGK (Colposcopy Working Group), and physicians representing gynecologists in private practice. The different scientific associations nominated representatives, who attended the various meetings. After an in-depth analysis of the recent literature, three meetings and numerous votes by telephone, we were able to achieve a consensus about the contents of this guideline. Recommendations The guideline provides recommendations for the diagnosis and treatment of CIN which take account of the gynecological cytology nomenclature used in Austria.
Published: 2018
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29. Interdisciplinary Diagnosis, Therapy and Follow-up of Patients with Endometrial Cancer. Guideline (S3-Level, AWMF Registry Number 032/034-OL, April 2018) – Part 2 with Recommendations on the Therapy and Follow-up of Endometrial Cancer, Palliative Care, Psycho-oncological/Psychosocial Care/Rehabilitation/Patient Information and Healthcare Facilities

Author: Ingo B. Runnebaum, Thomas Langer, Eric Steiner, Monika Nothacker, Christian Kurzeder, Günter Emons, Volker Hagen, Heinrich Prömpeler, Heike Raatz, Rita K. Schmutzler, Simone Wesselmann, Anne Letsch, Susanne Blödt, Michael D. Mueller, Joachim Weis, Nina Bock, M. Gebhardt, Edgar Petru, Christoph Uleer, Stefan Aretz, Jan Langrehr, Olaf Ortmann, Peter Mallmann, Dirk Vordermark, Wolfgang Cremer, Markus Follmann, Reina Tholen, Saskia Erdogan, Petra Feyer, Matthias W. Beckmann, Ludwig Kiesel, Peter Niehoff, Ralf Witteler, Michael Friedrich, Anne Derke Rose, Felix Hilpert, Clemens B. Tempfer, Nils Rahner, Werner Lichtenegger, Ulla Henscher, Vratislav Strnad, Franz-Josef Prott, Gerd Bauerschmitz, Rainer Kimmig, Doris Mayr, Jutta Hübner, Volker Hanf, Edward Wight, Kerstin Paradies, Jan Menke, Joan Elisabeth Panke, Timm Dauelsberg, Birgitt van Oorschot, I Juhasz-Boess, Gerlinde Egerer, Lars-Christian Horn, Michael Kreißl, Christiane Niehues, M Fleisch, Alexander Mustea, Annemarie Schorsch, Alain G. Zeimet, Verena Steinke-Lange, Alfons Meindl, Steffen Leinung, Stefan Höcht, Dieter Grab, Michael Reinhardt, Bernd Alt-Epping, and Sigurd Lax
Subjects: precancers, medicine.medical_specialty, Palliative care, medicine.medical_treatment, Endometriumkarzinom, Medizin, Guideline/Leitlinie, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Maternity and Midwifery, Health care, medicine, follow up, GebFra Science, 030212 general & internal medicine, Präkanzerosen, Intensive care medicine, Leitlinie, therapy, business.industry, Endometrial cancer, Obstetrics and Gynecology, Cancer, Guideline, medicine.disease, 3. Good health, Radiation therapy, 030220 oncology & carcinogenesis, endometrial cancer, Nachsorge, Therapie, business, guideline
Abstract: Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose Using evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patientʼs quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal extent of surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy if required. An evidence-based optimal use of different therapeutic modalities should improve the survival rates and quality of life of these patients. This S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources included reviews of evidence, which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one part of the guideline. Identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then subsequently modified during structured consensus conferences and/or additionally amended online using the DELPHI method, with consent between members achieved online. The guideline report is freely available online. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of endometrial cancer including precancers and early endometrial cancer as well as recommendations on palliative medicine, psycho-oncology, rehabilitation, patient information and healthcare facilities to treat endometrial cancer. The management of precancers of early endometrial precancerous conditions including fertility-preserving strategies is presented. The concept used for surgical primary therapy of endometrial cancer is described. Radiotherapy and adjuvant medical therapy to treat endometrial cancer and uterine carcinosarcomas are described. Recommendations are given for the follow-up care of endometrial cancer, recurrence and metastasis. Palliative medicine, psycho-oncology including psychosocial care, and patient information and rehabilitation are presented. Finally, the care algorithm and quality assurance steps for the diagnosis, therapy and follow-up of patients with endometrial cancer are outlined.
Published: 2018
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30. Adjuvante Therapie des Endometriumkarzinoms

Author: Dirk Vordermark, Stefan Höcht, Anne Letsch, Edgar Petru, Peter Mallmann, Petra Feyer, Volker Hagen, and Alain G. Zeimet
Subjects: Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, 030220 oncology & carcinogenesis, medicine, Obstetrics and Gynecology, 030212 general & internal medicine, business
Abstract: Im April 2018 erschien die erste deutsche interdisziplinare S3-Leitlinie fur die Diagnostik, Therapie und Nachsorge der Patientinnen mit Endometriumkarzinom. Dieser Beitrag ist die Zusammenfassung der Kap. 7, „Strahlentherapie des Endometriumkarzinoms“, und 8, „Adjuvante medikamentose Therapie des Endometriumkarzinoms“, mit dem Ziel, dem Leser eine klinisch orientierte Kurzfassung an die Hand zu geben. Dargestellt sind die Empfehlungen zur postoperativen Brachy- und externen Strahlentherapie sowie zur Gestagen- und Chemotherapie bei Endometriumkarzinom Typ I und II einschlieslich der Karzinosarkome.
Published: 2018
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31. BRCA1 and BRCA2 mRNA-expression prove to be of clinical impact in ovarian cancer

Author: Sigurd Lax, Christian Marth, S Wenzel, C Degasper, I Tsibulak, Alain G. Zeimet, H Fiegl, Susanne Sprung, Verena Wieser, and Giridhar Shivalingaiah
Subjects: Adult, 0301 basic medicine, Cancer Research, medicine.medical_specialty, endocrine system diseases, medicine.medical_treatment, Mrna expression, Context (language use), Carcinoma, Ovarian Epithelial, Gastroenterology, Article, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Ovarian cancer, Internal medicine, medicine, Carcinoma, Humans, skin and connective tissue diseases, Aged, Platinum, Aged, 80 and over, BRCA2 Protein, Ovarian Neoplasms, Chemotherapy, Molecular medicine, BRCA1 Protein, business.industry, Gene Expression Profiling, Case-control study, Cytoreduction Surgical Procedures, Translational research, Middle Aged, Prognosis, medicine.disease, DNA Damage Repair, Up-Regulation, Gene Expression Regulation, Neoplastic, Serous fluid, Treatment Outcome, 030104 developmental biology, Oncology, Case-Control Studies, 030220 oncology & carcinogenesis, Mutation, Female, business
Abstract: Background Mutations in BRCA1 and BRCA2 are associated with better survival in ovarian cancer (OC) patients due to a better response to platinum-based chemotherapy. However, the impact of the BRCA1/2 mRNA-expression is not well characterized in OC. Patients and methods We investigated BRCA1/2 mRNA-expression in 12 non-neoplastic fallopian tubes and 201 epithelial OCs in relation to their clinical characteristics. Results We found higher BRCA1/2 mRNA-expression in OCs compared to controls (P = 0.011, P
Published: 2018
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32. Evaluation of Vav3.1 as prognostic marker in endometrial cancer

Author: Heidi Fiegl, Annemarie Wiedemair, Julia Rössler, Jiri Hatina, Dominik Wolf, Sieghart Sopper, Alain G. Zeimet, Daniel Reimer, Christian Marth, and Maximilian Boesch
Subjects: Adult, 0301 basic medicine, Oncology, VAV3, Cancer Research, medicine.medical_specialty, Original Article – Clinical Oncology, Endometrium, Protein isoform, 03 medical and health sciences, 0302 clinical medicine, Endometrial cancer, Internal medicine, Biomarkers, Tumor, medicine, Humans, Protein Isoforms, Stage (cooking), Proto-Oncogene Proteins c-vav, Cancer, Aged, Retrospective Studies, Aged, 80 and over, Hematology, Transcript variant, business.industry, General Medicine, Vav3, Middle Aged, Prognosis, medicine.disease, Combined Modality Therapy, Cystadenocarcinoma, Serous, Endometrial Neoplasms, Survival Rate, 030104 developmental biology, medicine.anatomical_structure, Case-Control Studies, 030220 oncology & carcinogenesis, Female, Guanine nucleotide exchange factor, business, Ovarian cancer, Adenocarcinoma, Clear Cell, Follow-Up Studies
Abstract: Purpose Vav3 is a guanine nucleotide exchange factor that regulates the activity of Rho/Rac family GTPases. In a study on ovarian cancer, we recently demonstrated pronounced prognostic and predictive value of Vav3.1, a specific truncation variant of the parental Vav3 gene. Here, we sought to investigate the role of Vav3.1 in the most prevalent gynecological tumor entity, endometrial cancer. Methods Vav3.1 transcript levels were determined in a large cohort of endometrial cancer patients using variant-specific PCR (n = 239), and non-malignant endometrial tissue served as control (n = 26). Expression levels of Vav3.1 were stratified according to established clinicopathological characteristics and correlated to long-term patient survival (average follow-up of > 7.5 years). Type 1 and type 2 cancers were separately investigated. Results While Vav3.1 was markedly overexpressed in endometrial cancer tissue, we could not detect associations with clinical parameters related to prognosis, such as FIGO stage and tumor grade. Kaplan–Meier estimators of different measures of survival failed to show prognostic significance of Vav3.1 in endometrial cancer. Lack of prognostic value was observed for both type 1 and type 2 cancers. Conclusions Our study shows that Vav3.1 is not suited as a marker of cancer progression and/or treatment response in endometrial cancer. Feasibility and potential benefit of targeting Vav3.1 in endometrial cancer needs to be evaluated in future studies, proceeding from its clear, roughly ten-fold, induction in the malignant endometrium.
Published: 2018
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33. BRCA1/2 and TP53 mutation status associates with PD-1 and PD-L1 expression in ovarian cancer

Author: Alain G. Zeimet, M Fleischer, Soeren Wenzel, Verena Wieser, H Fiegl, I Gaugg, Susanne Sprung, Christian Marth, Giridhar Shivalingaiah, and Sigurd Lax
Subjects: 0301 basic medicine, PD-L1, medicine.medical_specialty, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Obstetrics and gynaecology, BRCA1/2, PD-1, medicine, Gynecology, Univariate analysis, biology, business.industry, medicine.disease, Serous fluid, 030104 developmental biology, ovarian cancer, Oncology, 030220 oncology & carcinogenesis, Cohort, biology.protein, business, Ovarian cancer, Clear cell, Research Paper, IFNγ
Abstract: // Verena Wieser 1 , Inge Gaugg 1 , Martina Fleischer 1 , Giridhar Shivalingaiah 2, 5 , Soeren Wenzel 2 , Susanne Sprung 3 , Sigurd F. Lax 4 , Alain G. Zeimet 1 , Heidelinde Fiegl 1 and Christian Marth 1 1 Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck 6020, Austria 2 Division of Human Genetics, Medical University of Innsbruck, Innsbruck 6020, Austria 3 Institute of Pathology, Medical University of Innsbruck, Innsbruck 6020, Austria 4 Department of Pathology, Hospital Graz Sud-West, Academic Teaching Hospital of the Medical University Graz, Graz 8020, Austria 5 Present address: Division Biological Chemistry, Biocenter, Innsbruck, Medical University of Innsbruck, Innsbruck 6020, Austria Correspondence to: Heidelinde Fiegl, email: Heidelinde.Fiegl@i-med.ac.at Keywords: ovarian cancer; PD-1; PD-L1; IFNγ; BRCA1/2 Received: July 31, 2017 Accepted: February 27, 2018 Published: April 03, 2018 ABSTRACT Checkpoint molecules such as programmed cell death protein-1 (PD-1) and its ligand PD-L1 are critically required for tumor immune escape. The objective of this study was to investigate tumoral PD-1 and PD-L1 mRNA-expression in a cohort of ovarian cancer (OC) patients in relation to tumor mutations. We analyzed mRNA expression of PD-1 , PD-L1 and IFNG by quantitative real-time PCR in tissue of 170 patients with low grade-serous (LGSOC), high-grade serous (HGSOC), endometrioid and clear cell OC compared to 28 non-diseased tissues (ovaries and fallopian tubes) in relation to tumor protein 53 ( TP53 ) and breast cancer gene 1/2 ( BRCA1/2 ) mutation status. TP53 -mutated OC strongly expressed PD-L1 compared to TP53 wild-type OC ( p = 0.028) and BRCA1/2 -mutated OC increasingly expressed PD-1 ( p = 0.024) and PD-L1 ( p = 0.012) compared to BRCA1/2 wild-type OC. For the first time in human, we noted a strong correlation between tumoral IFNG and PD-1 or PD-L1 mRNA-expression, respectively ( p < 0.001). OC tissue increasingly expressed PD-1 compared to healthy controls (vs. ovaries: p < 0.001; vs. tubes: p = 0.018). PD-1 and PD-L1 mRNA-expression increased with higher tumor grade ( p = 0.008 and p = 0.027, respectively) and younger age (< median age, p = 0.001). Finally, in the major subgroup of our cohort, FIGO stage III/IV HGSOC, high PD-1 and PD-L1 mRNA-expression was associated with reduced progression-free ( p = 0.024) and overall survival ( p = 0.049) but only in the univariate analysis. Our study suggests that in OC PD-1 / PD-L1 mRNA-expression is controlled by IFNγ and affected by TP53 and BRCA1/2 mutations. We suggest that these mutations might serve as potential predictive factors that guide anti- PD1 / PD-L1 immunotherapy.
Published: 2018

34. Expression III: patients’ expectations and preferences regarding physician–patient relationship and clinical management—results of the international NOGGO/ENGOT-ov4-GCIG study in 1830 ovarian cancer patients from European countries

Author: A. du Bois, Jean-Emmanuel Kurtz, M. Keller, M. Jedryka, Florence Joly, Sabrina Chiara Cecere, Gennaro Cormio, Jalid Sehouli, Michael Friedlander, Antonio Casado, Catalin Vlad, Radoslav Chekerov, Daniel Reimer, E Van Nieuwenhuysen, Rolf Richter, Ignace Vergote, Cesar Mendiola, Alain G. Zeimet, G. Oskay-Özcelik, S Alavi, M. Maciejewski, and Patriciu Achimas-Cadariu
Subjects: Adult, medicine.medical_specialty, Patients, medicine.medical_treatment, MEDLINE, Disease, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Internal medicine, Recurrent disease, Humans, Medicine, Physician patient relationship, 030212 general & internal medicine, Aged, Ovarian Neoplasms, Health Services Needs and Demand, Physician-Patient Relations, Chemotherapy, business.industry, Hematology, Middle Aged, medicine.disease, Europe, Clinical trial, Oncology, 030220 oncology & carcinogenesis, Doctor–patient relationship, Female, business, Ovarian cancer
Abstract: Backround The primary aim of this study was to investigate information needs and treatment preferences of patients with ovarian cancer, focusing especially on physician–patient relationship and treatment. Patients and methods A questionnaire was developed based on the experiences of the national German survey ‘Expression II’, and was provided to patients with ovarian cancer either at initial diagnosis or with recurrent disease via Internet (online-version) or as print-out-version. Results From December 2009 to October 2012, a total of 1830 patients with ovarian cancer from eight European countries (Austria, Belgium, France, Germany, Italy, Poland, Romania, Spain) participated, 902 (49.3%) after initial diagnosis and 731 (39.9%) with recurrent ovarian cancer. The median age was 58 years (range 17–89). Nearly all patients (96.2%) had experienced upfront surgery followed by first-line chemotherapy (91.8%). The majority of patients were satisfied with the completeness and comprehensibility of the explanation about the diagnosis and treatment options. The three most important aspects, identified by patients to improve the treatment for ovarian cancer included: ‘the therapy should not induce alopecia’ (42%), ‘there must be more done to counter fatigue’ (34.5%) and ‘the therapy should be more effective’ (29.7%). Out of 659 (36%) patients, who were offered participation in a clinical trial, 476 (26%) were included. Conclusion This study underlines the high need of patients with ovarian cancer for all details concerning treatment options irrespective of their cultural background, the stage of disease and the patient’s age. Increased information requirements regarding potential side effects and treatment alternatives were recorded. Besides the need for more effective therapy, alopecia and fatigue are the most important side effects of concern to patients.
Published: 2018
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35. Truncated isoform Vav3.1 is highly expressed in ovarian cancer stem cells and clinically relevant in predicting prognosis and platinum-response

Author: Hubert Hackl, Maximilian Boesch, Jiri Hatina, Christian Marth, Alain G. Zeimet, Dominik Wolf, Walther Parson, Sieghart Sopper, Daniel Reimer, and Peter Altevogt
Subjects: 0301 basic medicine, VAV3, Cancer Research, VAV1, medicine.diagnostic_test, Cancer, Biology, medicine.disease, Flow cytometry, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, Cancer stem cell, 030220 oncology & carcinogenesis, Gene expression, medicine, Cancer research, Stem cell, Ovarian cancer
Abstract: Vav3 is a key modulator of GTP-hydrolases of the Rho/Rac family, which are crucially involved in cell proliferation. Vav3 is alternatively spliced in full-length Vav3-alpha and N-terminal truncated Vav3.1 lacking its self-regulatory domains. The aim of our study was to estimate the clinical impact of Vav3 and all other Vav family members in ovarian cancer. Purification of a stem-cell like side-population (SP) from ovarian cancer cell lines was performed by flow cytometry/FACS. Differences in gene expression between SP and NSP were assessed by Gene Array analysis and confirmed by RT-PCR and immunoblot. In addition, Vav mRNA expression was determined in 150 epithelial ovarian cancers. Clinicopathological parameters, platinum-sensitivity and survival were analyzed and associated with Vav expression. SP fractions of ovarian cancer cell lines exhibited marked overexpression of Vav3.1 (p
Published: 2017
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36. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG): clinical trial design for rare ovarian tumours

Author: I.L. Ray-Coquard, Alexandra Leary, Aikou Okamoto, Michael A. Quinn, Stephen Welch, T. Sugiyama, Keiichi Fujiwara, D. Provencher, Monica Bacon, Anneke M. Westermann, William Small, Kazunori Ochiai, Alain G. Zeimet, R.M. Glasspool, David Millan, E. Gomez-Garcia, Gavin Stuart, Nicoletta Colombo, Elise C. Kohn, Robert L. Coleman, Leary, A, Quinn, M, Fujiwara, K, Coleman, R, Kohn, E, Sugiyama, T, Glasspool, R, Ray Coquard, I, Colombo, N, Bacon, M, Zeimet, A, Westermann, A, Gomez Garcia, E, Provencher, D, Welch, S, Small, W, Millan, D, Okamoto, A, Stuart, G, and Ochiai, K
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, endocrine system diseases, Reviews, Translational research, Bleomycin, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, Etoposide, Ovarian Neoplasms, business.industry, Clinical study design, Hematology, Rare ovarian tumour, medicine.disease, female genital diseases and pregnancy complications, Clinical trial, Serous fluid, 030104 developmental biology, rare ovarian tumours, chemistry, Research Design, 030220 oncology & carcinogenesis, Female, business, Ovarian cancer, medicine.drug
Abstract: This manuscript reports the consensus statements on designing clinical trials in rare ovarian tumours reached at the fifth Ovarian Cancer Consensus Conference (OCCC) held in Tokyo, November 2015. Three important questions were identified concerning rare ovarian tumours (rare epithelial ovarian cancers (eOC), sex-cord stromal tumours (SCST) and germ cell tumours (GCT)): (i) What are the research and trial issues that are unique to rare ovarian tumours? There is a lack of randomised phase III data defining standards of care which makes it difficult to define control arms, but identifies unmet needs that merit investigation. Internationally agreed upon diagnostic criteria, expert pathological review and translational research are crucial. (ii) What should be investigated in rare eOC, GCT and SCST? Trials dedicated to each rare ovarian tumour should be encouraged. Nonetheless, where the question is relevant, rare eOC can be included in eOC trials but with rigorous stratification. Although there is emerging evidence suggesting that rare eOC have different molecular profiles, trials are needed to define new type-specific standards for each rare eOC (clear cell, low grade serous and mucinous). For GCTs, a priority is reducing toxicities from treatment while maintaining cure rates. Both a robust prognostic scoring system and more effective treatments for de novo poor prognosis and relapsed GCTs are needed. For SCSTs, validated prognostic markers as well as alternatives to the current standard of bleomycin/etoposide/cisplatin (BEP) should be identified. (iii) Are randomised trials feasible? Randomised controlled trials (RCT) should be feasible in any of the rare tumours through international collaboration. Ongoing trials have already demonstrated the feasibility of RCT in rare eOC and SCST. Mucinous OC may be considered for inclusion, stratified, into RCTs of non-gynaecological mucinous tumours, while RCTs in high risk or relapsed GCT may be carried out as a subset of male and/or paediatric germ cell studies.
Published: 2017
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37. TNFα signalling predicts poor prognosis of patients with endometrial cancer

Author: Alain G. Zeimet, J Kögl, Susanne Sprung, Verena Wieser, H Fiegl, Samira Abdel Azim, K Knoll, Christian Marth, and Hubert Hackl
Subjects: Oncology, Adult, Cancer Research, medicine.medical_specialty, Transcription, Genetic, medicine.drug_class, Regulator, Datasets as Topic, Inflammation, Mediator, Internal medicine, medicine, Humans, Aged, Aged, 80 and over, business.industry, Tumor Necrosis Factor-alpha, Endometrial cancer, Proteins, General Medicine, Middle Aged, medicine.disease, Prognosis, Endometrial Neoplasms, Estrogen, Cohort, Tumor necrosis factor alpha, Female, medicine.symptom, Signal transduction, business, Signal Transduction
Abstract: Endometrial cancer (EC) is the most common gynaecologic tumour in the Western world. Previous studies have implicated an imbalance of oestrogens and progestogens in the development of most ECs, while the role of low-grade tissue inflammation remains largely unexplored. We investigated the impact of tumour necrosis factor alpha (TNFα), a central mediator of inflammation and spermatogenesis-associated protein 2 (SPATA2), a regulator of TNF receptor signalling, on clinical outcomes in EC. We evaluated TNFA and SPATA2 transcript levels in 239 EC patients and 25 non-malignant control tissues. Findings were validated in a cohort of 332 EC patients from The Cancer Genome Atlas (TCGA). Expression of TNFA and SPATA2 was increased in EC when compared with control tissues (P < 0.001). TNFA expression correlated with SPATA2 expression in non-malignant (P = 0.003, rS = 0.568) and EC tissue (P = 0.005, rS = 0.179). High TNFA and SPATA2 expression were associated with poor recurrence-free survival (RFS; P = 0.049 and P = 0.018) and disease-specific (P = 0.034 and P = 0.002) survival. Increased SPATA2 expression was also associated with decreased overall survival (OS; P = 0.013). In multivariate analysis, both TNFA and SPATA2 were predictors of clinical outcome. The impact of SPATA2 on RFS and OS could be validated in the TCGA cohort. Our study demonstrates that ECs exhibit a TNF signature which predicts clinical outcome. These findings indicate that TNF signalling modulates the course of EC, which could be therapeutically utilized in the future.
Published: 2020

38. Correction to: Epigenetic regulation of L1CAM in endometrial carcinoma: comparison to cancer–testis (CT-X) antigens

Author: Alain G. Zeimet, Peter Altevogt, Heidi Fiegl, Marco Pfeifer, Verena Tischler, Elisabeth Müller-Holzner, Uwe Schirmer, Peter K. Bode, University of Zurich, and Altevogt, Peter
Subjects: 0301 basic medicine, Cancer Research, Pathology, medicine.medical_specialty, L1, 610 Medicine & health, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Antigen, 1311 Genetics, 10049 Institute of Pathology and Molecular Pathology, Genetics, Carcinoma, medicine, 1306 Cancer Research, Epigenetics, Testis cancer, business.industry, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Staining, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, 2730 Oncology, business
Abstract: Following publication of the original article [1], we have been alerted to errors in Figs. 2 and 8. In Fig. 2B, the GAPDH loading control for Hec1A cells is shown twice in error (in Fig. 2B and Fig. 2C). In Fig. 8, in testis case 1 (first column) the MAGE-A4 staining panel was repeated and also appears as the NY-ESO-1 staining panel in error. The corrected versions of Fig. 2 and Fig. 8 are shown below. We apologize for this inconvenience.
Published: 2018
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39. Enlarged cardiophrenic lymph nodes predict disease involvement of the upper abdomen and the outcome of primary surgical debulking in advanced ovarian cancer

Author: Friedrich Aigner, Fabian Steinkohl, Daniel Reimer, Christian Marth, Alain G. Zeimet, Anna Luger, and Werner Jaschke
Subjects: medicine.medical_specialty, 03 medical and health sciences, 0302 clinical medicine, Paraaortic lymph nodes, Ascites, Medicine, Humans, 030212 general & internal medicine, Original Research Article, Stage (cooking), prognostic impact, Aged, Neoplasm Staging, Retrospective Studies, Ovarian Neoplasms, 030219 obstetrics & reproductive medicine, predictive value, business.industry, Hazard ratio, Obstetrics and Gynecology, General Medicine, Cytoreduction Surgical Procedures, Middle Aged, Debulking, medicine.disease, Prognosis, cardiophrenic lymph node, Tumor Debulking, ovarian cancer, Cardiophrenic Lymph Node, Oncology, Abdominal Neoplasms, Lymphatic Metastasis, residual disease, Female, Radiology, medicine.symptom, business, Ovarian cancer, Tomography, X-Ray Computed
Abstract: Introduction The outcome of ovarian cancer patients is highly dependent on the success of primary debulking surgery in terms of postoperative residual disease. This study critically evaluates the clinical impact of preoperative radiologic assessment of the cardiophrenic lymph node (CPLN) status in advanced ovarian cancer. Material and methods Baseline CT scans of 178 stage III and IV ovarian cancer patients were retrospectively reviewed by two independent radiologists. CPLN enlargement defined at a short‐axis ≥5 mm was evaluated for its prognostic value and predictive power of upper abdominal tumor involvement and the chance of complete intra‐abdominal tumor resection at primary debulking surgery. Only patients without surgically removed CPLN were eligible for this study. Results Enlarged CPLNs were detected in 50% of patients and correlated with radiologically suspicious (P = .028) and histologically confirmed (P = .001) paraaortic lymph node metastases. CPLNs ≥ 5 mm were associated with high CA‐125 levels at baseline and revealed independent prognostic relevance for progression‐free survival (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.33‐3.42) and overall survival (HR 2.18, 95% CI 1.16‐4.08). Noteworthy, patients with enlarged CPLNs nonetheless benefit from complete intra‐abdominal tumor debulking in terms of an improvement in progression‐free survival (HR 0.60, 95% CI 0.38‐0.94) and overall survival (HR 0.59, 95% CI 0.35‐0.82). Enlarged CPLNs correctly predicted carcinomatosis of the upper abdomen in 94.6%. A predictive score of complete tumor debulking, termed CD‐score, which integrates, beside a CPLN short axis
Published: 2019

40. TP53 mutations in cell-free DNA as early markers of therapeutic response in platinum-resistant relapsed ovarian cancer (PROC): a prospective translational analysis of the phase II GANNET53 clinical trial

Author: Sven Mahner, Pauline Wimberger, Jalid Sehouli, Eric Pujade-Lauraine, Alain G. Zeimet, Ute M. Moll, Florence Joly, P Combe, S Darb-Esfahani, Ioana Braicu, Regina Berger, E Van Nieuwenhuysen, Ignace Vergote, Christian Marth, Frédéric Selle, I.L. Ray-Coquard, P Busschaert, P. Harter, Robert Zeillinger, Barbara Schmalfeldt, A Vanderstichele, Nicole Concin, D Lambrechts, and Atanas Ignatov
Subjects: Oncology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Cancer, medicine.disease, Tp53 mutation, Clinical trial, Serous fluid, Internal medicine, Biopsy, medicine, Ovarian cancer, business, Genotyping, Platinum resistant
Abstract: Introduction/Background Detecting tumor-specific genetic alterations in cell-free DNA (cfDNA) obtained from cancer patients allows for a quantification of the tumoral fraction, i.e. the circulating tumor DNA (ctDNA). Previous studies in metastatic cancer patients showed that early changes of this fraction during therapy are indicative of therapeutic response. We tested this hypothesis on cfDNA samples collected in the GANNET53 clinical trial (FP7, funded by the European Commission, grant no 602602). Methodology Patients with high-grade serous/endometrioid and/or undifferentiated PROC were recruited for treatment with weekly paclitaxel with or without Hsp90-inhibitor ganetespib. Archival biopsy samples were used for tumor TP53 genotyping. CfDNA was prospectively collected prior to treatment at baseline (cycle 1 day 1, C1D1), 24 hours later (cycle 1 day 2, C1D2) and after 4 and 8 weeks, at day 1 of cycle 2 (C2D1) and 3 (C3D1) respectively. Targeted TP53 resequencing was performed on cfDNA and allelic frequencies of the known TP53 variant (TP53 VAF) were quantified and correlated with clinical outcome. Results For 125 of the 133 randomized patients, at least 1 C1D1 cfDNA sample was available. For 119 tumor samples, TP53 genotyping was successful and identified deleterious TP53 mutations in 106 patients (89.1%). The median ctDNA level was 1.82% (IQR:0.17–8.34%) at C1D1 which decreased significantly after 4–8 weeks of therapy. Overall, ctDNA was detectable in 64.6% (64/99) of baseline samples. Baseline CA125 did not differ between cases with and without detectable ctDNA at C1D1. Detection of ctDNA at C1D1 (HR 2.3; 95%CI:1.4–3.9), C1D2 (HR 2.2; 95%CI:1.3–3.9) and C2D1 (HR 2.8; 95%CI:1.6–4.9) predicted a worse overall survival. A subgroup of patients for whom TP53 ctDNA was undetectable at C2D1 or C3D1 (14/64) had a high overall response rate of 64.2%. Conclusion Quantification of TP53 mutations in cfDNA of PROC patients has prognostic value at baseline. Favorable early changes during treatment may predict therapeutic response. Disclosure The presenting author, A.Vanderstichele, has no conflict of interest.
Published: 2019
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41. Clinical Impact of RANK Signalling in Ovarian Cancer

Author: Johannes Haybaeck, Susanne Sprung, I Tsibulak, Hubert Hackl, Alain G. Zeimet, Christian Marth, Verena Wieser, and H Fiegl
Subjects: 0301 basic medicine, musculoskeletal diseases, Cancer Research, Stromal cell, lcsh:RC254-282, RANK, Article, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, medicine, Receptor, biology, business.industry, RANKL, RANK Ligand, denosumab, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 030104 developmental biology, Denosumab, ovarian cancer, Oncology, inflammation, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Tumor necrosis factor alpha, OPG, business, Ovarian cancer, medicine.drug
Abstract: Ovarian cancer (OC) is a gynaecological malignancy with poor clinical outcome and limited treatment options. The receptor activator of nuclear factor-&kappa, B (RANK) pathway, activated by RANK ligand (RANKL), critically controls bone metabolism, tumourigenesis and tumour immune responses. Denosumab, a monocloncal RANKL antibody, exerts tumour-suppressive effects in mice and humans. Here, we investigated the relevance of RANK signalling in OC. RANK, RANKL and OPG expression in 192 epithelial OC tissues was compared to expression in 35 non-malignant control tissues and related to clinico-pathological characteristics. Findings were validated in a cohort of 563 OC patients from The Cancer Genome Atlas (TCGA). The expression of RANK, RANKL and OPG was studied in four OC cell lines and the impact of RANK ligation or blockade on OC cell proliferation was determined. RANK, RANKL and OPG were expressed in epithelial and stromal cells in OC. RANKL expression was elevated in OC tissue, particularly in BRCA1/2 mutated tumours. High RANKL expression independently predicted reduced progression-free (PFS, p = 0.017) and overall survival (OS, p = 0.007), which could be validated in the TCGA cohort (PFS, p = 0.022, OS, p = 0.046, respectively). Expression of RANK and OPG in OC cells was induced by inflammatory cytokines IL-1&beta, and TNF&alpha, Neither recombinant RANK ligation nor denosumab treatment affected OC cell proliferation. Our study independently links RANKL expression with poor clinical outcome in two unrelated OC cohorts. These findings implicate RANK signalling in the immunopathogenesis of OC and warrant clinical trials with denosumab in OC.
Published: 2019

42. Part I of GANNET53: A European Multicenter Phase I/II Trial of the Hsp90 Inhibitor Ganetespib Combined With Weekly Paclitaxel in Women With High-Grade, Platinum-Resistant Epithelial Ovarian Cancer-A Study of the GANNET53 Consortium

Author: Nicole Concin, Philippe A. Cassier, Jalid Sehouli, Regina Berger, Hanno Ulmer, Eric Pujade-Lauraine, Alain G. Zeimet, Ute M. Moll, Karin Leunen, Ignace Vergote, Ioana Braicu, Isabelle Ray-Coquard, Christian Marth, and Sven Mahner
Subjects: 0301 basic medicine, medicine.medical_specialty, Cancer Research, CARCINOMA, Nausea, medicine.medical_treatment, ganetespib, Ganetespib, Neutropenia, lcsh:RC254-282, THERAPY, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, Hsp90 inhibitors, p53 mutation, platinum-resistance, recurrent ovarian carcinoma, 0302 clinical medicine, MOUSE MODELS, Internal medicine, medicine, DOSE-ESCALATION, Adverse effect, MUTANT P53, Chemotherapy, Science & Technology, business.industry, PROTEIN 90 INHIBITOR, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Clinical Trial, PEGYLATED LIPOSOMAL DOXORUBICIN, 3. Good health, 030104 developmental biology, Paclitaxel, chemistry, Oncology, 030220 oncology & carcinogenesis, SURVIVAL, GAIN, medicine.symptom, Ovarian cancer, business, Life Sciences & Biomedicine, Progressive disease
Abstract: Background: Stabilized mutant p53 protein (mutp53) is a novel target in epithelial ovarian cancer. Due to aberrant conformation, mutp53 proteins depend on folding support by the Hsp90 chaperone. Hsp90 blockade induces degradation of mutp53, resulting in tumor cell cytotoxicity and increased sensitivity to chemotherapeutics. Preclinical synergy of the Hsp90 inhibitor ganetespib combined with paclitaxel provided the rationale for testing the combination in platinum-resistant ovarian cancer (PROC) patients in the GANNET53 trial (NCT02012192). Methods: Eligible patients had high-grade PROC with ≤ 4 prior lines of chemotherapy. Weekly paclitaxel (80 mg/m2) and increasing doses of ganetespib (100, 150 mg/m2) were given i.v. on days 1, 8, 15 in a 28 days cycle until disease progression or unacceptable toxicity. Endpoints were safety and determination of phase II dose. Dose limiting toxicity (DLT) was defined as grade 4 toxicity (with exceptions) occurring in cycles 1&2. Results: Ten patients (median age 59 years; range 43-70) were enrolled. No DLT occurred in cohort 1 (4 patients treated with paclitaxel + ganetespib 100 mg/m2), nor in cohorts 2 and 3 (6 patients treated with paclitaxel + ganetespib 150 mg/m2). The most common adverse event (AE) related to ganetespib was transient grade 1/2 diarrhea (n = 6). Related grade 1/2 AEs in >2 patients included QTc prolongation (n = 4), nausea (n = 3), anemia (n = 3), headache (n = 3), fatigue (n = 3), and dyspnoea (n = 3). Most frequently related grade 3/4 AEs were diarrhea (n = 3) and neutropenia (n = 2). There was 1 death on study due to hemorrhage from a duodenal ulcer. Three patients discontinued study treatment due to serious AEs (digestive hemorrhage n = 1, cardiac failure n = 1, abdominal pain and vomiting n = 1), 6 due to progressive disease, one due to investigator and patient decision. Two patients achieved a partial response (ORR 20%) and 4 patients a stable disease (disease control rate of 60%). Median PFS was 2.9 months (1.6 months in cohort 1 at 100 mg/m2 ganetespib, 5.1 months in cohorts 2+3 at 150 mg/m2 ganetespib). Conclusions: The combination of ganetespib 150 mg/m2 with paclitaxel 80 mg/m2 once weekly for 3 out of 4 weeks was generally well-tolerated with no DLTs, and therefore chosen for the randomized phase II trial. ispartof: FRONTIERS IN ONCOLOGY vol:9 ispartof: location:Switzerland status: published
Published: 2019

43. Abstract 947: Effects of methadone on ovarian cancer cell-lines and patient-derived tumor-spheroids

Author: Olli Carpén, Beata Seeber, Michael J. Ausserlechner, Alain G. Zeimet, Judith Hagenbuchner, Elisabeth Reiser, Kaisa Huhtinen, Verena Wieser, Julia Roessler, Christian Marth, Sieghart Sopper, H Fiegl, I Tsibulak, Christiana Kyvelidou, and Walther Parson
Subjects: Cisplatin, Agonist, Cancer Research, medicine.drug_class, Cell growth, business.industry, Cancer, Pharmacology, medicine.disease, 3. Good health, Oncology, Apoptosis, medicine, Cytotoxic T cell, business, Ovarian cancer, medicine.drug, Methadone
Abstract: Background: D,L-Methadone exerts analgesic effects via the mu opioid receptor, encoded by OPRM1 and therefore plays a role in chronic pain management. Although the use of this opioid-receptor agonist as an anti-cancer drug is deemed controversial, this drug is gaining popularity in Europe as an “off-label” therapy despite insufficient research to support its benefits. In preclinical glioblastoma and leukaemia cell culture models D,L-methadone showed apoptotic and chemo-sensitizing effects. Its effects in ovarian cancer (OC) are completely unexplored. Methods: We analysed the OPRM mRNA expression in six cisplatin-sensitive, two cisplatin-resistant OC cell-lines, 192 OC samples and 12 non-neoplastic control tissues. Pro-angiogenetic, cytotoxic and apoptotic effects of D,L-methadone were evaluated in OC cell-lines and four patient-derived tumor-spheroid models. Results: OPRM1 was transcriptionally expressed in 69% of OC-tissues and in five of eight OC cell-lines. D,L-methadone exposure significantly reduced cell-viability in five OC cell-lines irrespective of OPRM1 expression. D,L-methadone, applied alone or combined with cisplatin, showed no significant effects on apoptosis or VEGF secretion in cell-lines. Notably, in two of the four spheroid models, treatment with D,L-methadone resulted in significantly enhanced cell growth (by up to 121%), especially after long-term exposure. This is consistent with the observed attenuation of the inhibitory effects of cisplatin in three spheroid models when adding D,L-methadone. The effect of methadone treatment on VEGF secretion in tumor-spheroids was inconclusive. Conclusions: Our study demonstrates that certain OC samples express OPRM1, which, however, is not a prerequisite for D,L-methadone function. As such, D,L-methadone may exert detrimental effects by stimulating the growth of certain OC-cells and abrogating cisplatin's therapeutic effect. Citation Format: Heidelinde Fiegl, Judith Hagenbuchner, Michael J. Ausserlechner, Christiana Kyvelidou, Beata Seeber, Sieghart Sopper, Irina Tsibulak, Verena Wieser, Julia Roessler, Elisabeth Reiser, Kaisa Huhtinen, Olli Carpén, Walther Parson, Christian Marth, Alain G. Zeimet. Effects of methadone on ovarian cancer cell-lines and patient-derived tumor-spheroids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 947.
Published: 2021
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44. Evaluating L1CAM expression in human endometrial cancer using qRT-PCR

Author: Daniel Reimer, Heidi Fiegl, Annamarie Wiedermair, Christian Marth, Sara Notaro, Julia Rössler, Peter Altevogt, Michaela Duggan-Peer, and Alain G. Zeimet
Subjects: 0301 basic medicine, medicine.medical_specialty, Neural Cell Adhesion Molecule L1, Real-Time Polymerase Chain Reaction, Endometrium, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, medicine, Carcinoma, Humans, Promoter Regions, Genetic, Aged, Gynecology, business.industry, Endometrial cancer, Case-control study, Reproducibility of Results, Cancer, qRT-PCR, DNA Methylation, Middle Aged, medicine.disease, Immunohistochemistry, Endometrial Neoplasms, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Real-time polymerase chain reaction, Oncology, Case-Control Studies, L1CAM, 030220 oncology & carcinogenesis, endometrial cancer, DNA methylation, outcome, Female, methylation, Skin cancer, business, Follow-Up Studies, Research Paper
Abstract: // Sara Notaro 1, 2 , Daniel Reimer 1 , Michaela Duggan-Peer 1 , Heidi Fiegl 1 , Annamarie Wiedermair 1 , Julia Rossler 1 , Peter Altevogt 3, 4 , Christian Marth 1 , Alain Gustave Zeimet 1 1 Department of Gynecology and Obstetrics, Medical University of Innsbruck, Innsbruck, Austria 2 Department of Gynecology and Obstetrics, University of Brescia, Brescia, Italy 3 Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany 4 Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany Correspondence to: Alain Gustave Zeimet, email: alain.zeimet@uki.at Keywords: L1CAM, endometrial cancer, qRT-PCR, outcome, methylation Received: January 04, 2016 Accepted: May 08, 2016 Published: May 24, 2016 ABSTRACT Background: Management of endometrial carcinoma (EC) still needs improvement of risk assessment. Recently, L1CAM immunohistochemical (IHC) evaluation showed a unique value to predict the outcome of early EC. However IHC results are often conflicting for lack of inter-laboratory standardisation. Methods: Here, as a proof of concept and to increase reproducibility we assayed eighty-two EC and 26 normal endometrium samples for L1CAM expression (L1CAM EXP ) via qRT-PCR. The IHC evaluation was performed in 50 cancer samples. Moreover, we aimed to substantiate the in-vitro findings of L1CAM regulation through its promoter methylation (L1CAM MET ), miR-34a expression and miR-34a promoter methylation. DNA methylation was assessed with MethyLight PCR technique. Results : High overall concordant results between IHC and RT-PCR evaluations were found. L1CAM EXP was detected in 11% of cancer specimens. These positive cancers exhibited a worse DFS (p=0.032) and OS (p=0.016) in a multivariate COX-regression model. L1CAM EXP predicted distant failure (p=0.007) and L1CAM MET predicted risk-reduction of lymph-node involvement (p=0.005). Inverse correlations between L1CAM EXP and L1CAM MET (p=0.004) and between L1CAM EXP and miR-34a expression (p=0.002) were found. Conclusions: In conclusion qRT-PCR analysis is a reliable approach to evaluate L1CAM status in EC and L1CAM EXP was highly predictive for distant failure and poor outcome, confirming the large IHC-based studies. Interestingly, L1CAM MET was able to assess the risk of pelvic lymph-node involvement. Especially the latter finding has to be confirmed in larger prospective series.
Published: 2016
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45. Clinical impact of L1CAM expression measured on the transcriptome level in ovarian cancer

Author: Michaela Duggan-Peer, Daniel Reimer, Samira Abdel Azim, Christian Marth, Afschin Soleiman, Heidi Fiegl, Susanne Sprung, and Alain G. Zeimet
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, RT-PCR, Neural Cell Adhesion Molecule L1, Kaplan-Meier Estimate, Real-Time Polymerase Chain Reaction, survival, Disease-Free Survival, Targeted therapy, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Obstetrics and gynaecology, Internal medicine, Biomarkers, Tumor, medicine, Humans, RNA, Messenger, Survival analysis, Neoplasm Staging, Retrospective Studies, Ovarian Neoplasms, Gynecology, business.industry, Cancer, Middle Aged, Prognosis, targeted therapy, medicine.disease, Immunohistochemistry, ovarian cancer, 030104 developmental biology, Real-time polymerase chain reaction, Case-Control Studies, L1CAM, 030220 oncology & carcinogenesis, Disease Progression, Female, Neoplasm Grading, business, Ovarian cancer, Research Paper
Abstract: // Samira Abdel Azim 1 , Michaela Duggan-Peer 1 , Susanne Sprung 1 , Daniel Reimer 1 , Heidi Fiegl 1, 2 , Afschin Soleiman 1 , Christian Marth 1 , Alain G. Zeimet 1 1 Department of Obstetrics and Gynecology, Medical University of Innsbruck, 6020 Innsbruck, Austria 2 Department of Obstetrics and Gynecology, Laboratory for Clinical Biochemistry, Medical University of Innsbruck, 6020 Innsbruck, Austria Correspondence to: Alain G. Zeimet, email: alain.zeimet@tirol-kliniken.at , alain.zeimet@i-med.ac.at Keywords: ovarian cancer, L1CAM, targeted therapy, RT-PCR, survival Received: October 21, 2015 Accepted: April 18, 2016 Published: May 11, 2016 ABSTRACT Background: High expression of L1 cell adhesion molecules (L1CAM) has been repeatedly shown to be associated with aggressive disease behavior, which translates in poor clinical outcome in various cancer entities. However, in ovarian cancer results based either on immunohistochemistry or cytosolic protein quantifications remained conflicting regarding clinical behavior. In the present work we assessed L1CAM expression on the transcriptome level with the highly sensitive quantitative real-time PCR (qRT-PCR) to define its relevance in ovarian cancer biology. Results: There was a significant difference in L1CAM high and low mRNA expressing cancers with regard to disease-free (p=0.002) and overall survival (p=0.008). L1CAM proofed to be an independent predictor for disease progression (HR 1.8, p=0.01) and overall survival (HR 1.6, p=0.04). Furthermore, a significant positive correlation between the level of L1CAM and the grade of tumor differentiation (p=0.04), the FIGO stage (p=0.025) as well as the histological subtype (p= 0.002) was found. Methods: This study included fresh frozen tissue samples of 138 patients with FIGO I-IV stage ovarian cancer. L1CAM mRNA expression was determined using qRT-PCR. In the calculations special attention was put on the various histological subtypes. In survival analysis median L1CAM mRNA expression obtained in the entire cohort of ovarian cancer samples was used as a cut-off to distinguish between high and low L1CAM mRNA expression. Conclusion: L1CAM mRNA expression appears to play a substantial role in the pathophysiology of ovarian cancer that is translated into poor clinical outcome. Additionally humanized L1CAM antibodies, which can serve as potential future treatment options are under testing.
Published: 2016
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46. Ovarian Cancer Stem Cell Heterogeneity

Author: Dominik Wolf, Michaela Kripnerova, Sieghart Sopper, Daniel Reimer, Maximilian Boesch, Christian Marth, Jiri Hatina, and Alain G. Zeimet
Subjects: Cluster of differentiation, CD117, CD44, Wnt signaling pathway, Biology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Side population, Ovarian carcinoma, medicine, Cancer research, biology.protein, 030212 general & internal medicine, Stem cell, Ovarian cancer
Abstract: Ovarian carcinoma features pronounced clinical, histopathological, and molecular heterogeneity. There is good reason to believe that parts of this heterogeneity can be explained by differences in the respective cell of origin, with a self-renewing fallopian tube secretory cell being likely responsible for initiation of an overwhelming majority of high-grade serous ovarian carcinomas (i.e., type II tumors according to the recent dualistic classification), whereas there are several mutually non-exclusive possibilities for the initiation of type I tumors, including ovarian surface epithelium stem cells, endometrial cells, or even cells of extra-Mullerian origin. Interestingly, both fallopian tube self-renewing secretory cells and ovarian surface epithelium stem cells seem to be characterized by an overlapping array of stemness signaling pathways, especially Wnt/β-catenin. Apart from this variability in the respective cell of origin, the particular clinical behavior of ovarian carcinoma strongly suggests an underlying stem cell component with a crucial impact. This becomes especially evident in high-grade serous ovarian carcinomas treated with classical chemotherapy, which entails a gradual evolution of chemoresistant disease without any apparent selection of clones carrying obvious chemoresistance-associated mutations. Several cell surface markers (e.g., CD24, CD44, CD117, CD133, and ROR1) as well as functional approaches (ALDEFLUOR™ and side population assays) have been used to identify and characterize putative ovarian carcinoma stem cells. We have recently shown that side population cells exhibit marked heterogeneity on their own, which can hamper their straightforward therapeutic targeting. An alternative strategy for stemness-depleting interventions is to target the stem cell niche, i.e., the specific microanatomical structure that secures stem cell maintenance and survival through provision of a set of stem cell-promoting and differentiation-antagonizing factors. Besides identifying direct or indirect therapeutic targets, profiling of side population cells and other ovarian carcinoma stem cell subpopulations can reveal relevant prognostic markers, as exemplified by our recent discovery of the Vav3.1 transcript variant, which filters out a fraction of prognostically unfavorable ovarian carcinoma cases.
Published: 2019
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47. Intraperitoneale Chemotherapie in der Behandlung des Ovarial- und Tubenkarzinoms

Author: Christian Marth and Alain G. Zeimet
Abstract: Bei der intraperitonealen Chemotherapie handelt es sich um eine lokoregionare Tumorbehandlung mit bewiesenermasen effizienten Zytostatika, die uber mehrere Zyklen direkt in die freie Bauchhohle instilliert werden. Dies geschieht gewohnlich uber ein subkutan implantiertes Kathetersystem mit Reservoir. Eine wesentliche Voraussetzung fur die i.p.-Chemotherapie ist eine gleichmasige Verteilung der applizierten Zytostatika und somit eine freie Zugangigkeit zur gesamten Bauchhohle. Aus diesem Grund sind peritoneale Verwachsungen als Kontraindikation fur eine i.p.-Chemotherapie anzusehen. Das Ovarial- und das Tubenkarzinom eignen sich fur ein solches Vorgehen, da die tumorale Ausbreitung bei beiden Tumorentitaten meist auf das Cavum peritonei begrenzt bleibt. Prinzipiell konnen uber diesen Applikationsweg hohere Zytostatikadosen als bei einer konventionellen systemischen Therapie verabreicht werden. Es muss jedoch angenommen werden, dass ein Teil der i.p.-applizierten Dosis nach langsamer Resorption aus der Peritonealhohle auch eine systemische Wirkung entfaltet. Das ist nicht nur fur den antitumoralen Effekt, sondern auch fur das Auftreten von Nebenwirkungen von Bedeutung. Andererseits ist festzuhalten, dass die i.p.-applizierten Therapeutika, bezogen auf die Tumoroberflache, gewohnlich eine Eindringtiefe von 1–2 mm nicht uberschreiten.
Published: 2018
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48. Tumor necrosis factor receptor modulator spermatogenesis-associated protein 2 is a novel predictor of outcome in ovarian cancer

Author: C Degasper, Alain G. Zeimet, H Fiegl, Verena Wieser, Walther Parson, I Tsibulak, K Leitner, Christian Marth, and H Welponer
Subjects: 0301 basic medicine, Adult, tumor necrosis factor‐α, Cancer Research, Carcinogenesis, Interleukin-1beta, Inflammation, medicine.disease_cause, Inflammation and Virology, Receptors, Tumor Necrosis Factor, Pathogenesis, spermatogenesis‐associated protein 2, 03 medical and health sciences, Young Adult, 0302 clinical medicine, medicine, Humans, Spermatogenesis, Aged, Aged, 80 and over, Ovarian Neoplasms, business.industry, Tumor Necrosis Factor-alpha, Interleukin, Cancer, Proteins, General Medicine, Original Articles, Middle Aged, medicine.disease, Progression-Free Survival, Serous fluid, tumorigenesis, 030104 developmental biology, ovarian cancer, Oncology, inflammation, 030220 oncology & carcinogenesis, Cancer research, Tumor necrosis factor alpha, Female, Original Article, medicine.symptom, Ovarian cancer, business
Abstract: Inflammation plays a crucial role in the pathogenesis of cancer with tumor necrosis factor-α (TNF-α) as a key mediator. Recently, spermatogenesis-associated protein 2 (SPATA2) was identified as a TNF receptor modulator which is required for TNF-induced inflammation and apoptosis. The available data on TNF-α in ovarian cancer (OC) are inconsistent, and SPATA2 is completely uncharacterized in tumorigenesis. We analyzed expression of SPATA2 and TNFA by quantitative real-time polymerase chain reaction in tissues of 171 patients with low-grade serous (LGSOC), high-grade serous (HGSOC), endometrioid and clear cell OC compared with 28 non-malignant control tissues. We stimulated OC cells (OVCAR3) with pro-inflammatory (TNF-α, interleukin [IL]-1β) and mitogenic stimuli (IL-6, lysophosphatidic acid) to establish a direct effect between inflammatory signaling and SPATA2. Pro-inflammatory, but not mitogenic stimuli, potently induced SPATA2 expression in OC cells. Expression of TNFA and SPATA2 was higher in OC compared with control tissues (P = 0.010 and P = 0.001, respectively) and correlated with each other (P = 0.034, rs = 0.198). When compared with grade 1 cancers, SPATA2 was expressed higher in grade 2 and 3 tumors (P = 0.011) as well as in HGSOC compared with LGSOC (P = 0.024). Multivariate survival analyses revealed that OC with high SPATA2 expression were associated with reduced progression-free survival (P = 0.048) and overall survival (P < 0.001). In conclusion, SPATA2 expression is regulated by TNF-α and IL-1β and is found to independently affect clinical outcome in OC patients. These data implicate a role of SPATA2 in tumorigenesis which warrants further investigation in gynecological malignancies.
Published: 2018

49. Immunotherapy in ovarian cancer: fake news or the real deal?

Author: Christian Marth, I Tsibulak, Verena Wieser, and Alain G. Zeimet
Subjects: Adoptive cell transfer, medicine.medical_treatment, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antineoplastic Agents, Immunological, Cancer immunotherapy, Ovarian carcinoma, medicine, Humans, 030304 developmental biology, Ovarian Neoplasms, 0303 health sciences, business.industry, Melanoma, Obstetrics and Gynecology, Cancer, Immunotherapy, medicine.disease, Prognosis, Oncology, 030220 oncology & carcinogenesis, Cancer research, Female, Ovarian cancer, business
Abstract: Cancer immunotherapy has emerged as one of the most promising approaches in oncology, and comprises the activation of the immune system to induce tumor immune surveillance or to reverse the tumor immune escape. Different therapeutic strategies for ovarian carcinoma have evolved over the years. Already 30 years ago, the first clinical studies focused on modulating the tumor cytokine network with special attention to interferon-mediated immune responses. With the exploration of specific tumor antigens such as NY-ESO-1, which is expressed in ovarian carcinoma and other malignancies, the development of therapeutic cancer vaccines has been pursued initiating the era of personalized anti-cancer medicine. Almost at the same time, the adoptive transfer of genetically modified autologous tumor-reactive T-cells occurred, but response rates in ovarian carcinoma were disappointing. Today, probably the most promising therapeutic approach in this context is the blockade of immune checkpoints, such as programed cell death protein 1 (PD-1) and one of its ligands (PD-L1) or cytotoxic T-cell lymphocyte-associated antigen 4 (CTLA-4), which has demonstrated impressive response rates in malignant melanoma and non-small cell lung cancer. Despite increasing availability of treatment approaches that target tumor immune surveillance in ovarian carcinoma, selecting patient groups that particularly benefit from these treatment modalities is clinically challenging as predictive biomarkers are lacking. Here, we summarize different immunotherapy approaches in ovarian cancer and discuss why immunotherapy in ovarian cancer is still in its infancy.
Published: 2018

50. (Iso‐)form Matters: Differential Implication of Vav3 Variants in Ovarian Cancer

Author: Alain G. Zeimet, Maximilian Boesch, Dominik Wolf, Sieghart Sopper, and Daniel Reimer
Subjects: 0301 basic medicine, Protein isoform, VAV3, Ovarian Neoplasms, Cancer Research, business.industry, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, Cancer stem cell, 030220 oncology & carcinogenesis, Commentaries, Cancer research, Medicine, Guanine Nucleotide Exchange Factors, Humans, Protein Isoforms, Female, Guanine nucleotide exchange factor, business, Ovarian cancer, Proto-Oncogene Proteins c-vav, Differential (mathematics)
Abstract: This commentary discusses recent results on the role of Vav3 in malignancy, in an effort to begin to define the underlying mechanisms and tissue context by which Vav3 proteins, in particular Vav3.1, promote the progression of malignant diseases and further modulate the response to clinically relevant drugs.
Published: 2018

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