bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of vascular endothelial growth factor (VEGF) and hypoxia-inductible factor-1 alpha (HIF-1) expression on the prognosis of locally advanced cervical carcinoma (LACC) treated with radiochemotherapy.
Authors: Madani Julia , Eizaguirre Beatriz , Alonso Vicente , Puertolas Teresa , Millastre Esther , Polo Marques Eduardo , Lao Romera Juan , Herrero Ana , Anton Antonio 
Published: September 2018

e17023 Background: Combination of radiotherapy plus platinum-based chemotherapy (RT-CT) is considered the standard treatment in LACC. The risk of recurrence after local treatment is around 50-70%. The role of angiogenesis in tumor progression has been shown in large series. The aim of this study was to determinate the impact of the expression of VEGF and HIF-1 on disease-free survival (DFS) and overall survival (OS) in patients with LACC receiving RT-CT. Methods: Expression of VEGF and HIF–1 was assessed by an immunohistochemistry (IHC) assay in 115 cases. Inmunostainning was considered negative (< 10% of cells), slightly positive (< 25%), moderate (26%-50%) and strongly positive (> 50%). A univariate analysis was carried out for each variable using the log-rank test. Subsequently, a multivariate analysis was performed employing Cox’s proportional hazards model. Results: 115 patients (p) with LACC were included and received RT-CT between January/2003 and December/2012. IHC revealed absence of expression of VEGF in 12 (10,4%) cases, slightly positive in 34 (29,6%), moderate in 30 (26,1%) and strongly positive in 39 (33,9%). The expression of HIF-1 was negative in 63 (54,8%) cases and positive (weak or moderate) in 52 (45,2%). 76p (66,1%) showed a complete clinical response (CR), 26p (22,6%) partial response and 13p (11,3%) stable disease or progression. The median follow–up was 35 months (1-140). 56p (48,7%) relapsed. Univariate analysis indicate that ECOG > 1, tumor size ≥ 4,5 cm, FIGO stage III-IVA, lymph nodes positive, non CR, CA125 post-treatment ≥ 35 U/mL, hemoglobin levels <11 mg/dl (basal, nadir and post-treatment), strong expression VEGF and positive expression of HIF – 1 were all associated with a significant lower OS and DFS. In multivariate analysis strong expression of VEGF remained statistically significant, as tumor size, non CR and hemoglobin level post-treatment < 11g/dL. Conclusions: IHC-assessed strong expression of VEGF was independent prognostic factor of shorter OS and DFS in patients with LACC treated with RT-CT. IHC determination of VEGF could be useful in clinical practice.
Clinical effect of liver transaminase abnormalities after ablation of ovarian cancer.
Authors: Manahan Kelly J , Geisler John P. 
Published: September 2018

e17042 Background: At initial presentation, patients with ovarian cancer often have disease involving the upper abdomen and specifically the liver (surface or parenchyma). The object of this study was to 1) see the difference in liver enzyme levels in women getting tumor ablation involving the liver compared to women getting tumor ablation not involving the liver and to 2) see if any differences had a readily noticeable clinical effect. Methods: A series of twenty women with initial diagnosis of ovarian cancer undergoing primary cytoreduction with tumor ablation involving the liver were compared to twenty women with initial diagnosis of ovarian cancer undergoing primary cytoreduction and tumor ablation without involvement of the liver. The data were compared with Fisher’s exact, Chi-square or Mann-Whitney U as appropriate. Results: Women undergoing tumor ablation involving the liver compared with women undergoing tumor ablation not involving the liver had significantly elevated AST and ALT levels the first day after surgery (p = 0.002; 0.002, respectively). There were no significant differences in age, operative blood loss or need for transfusion (p=0.24; 0.065; 0.33, respectively). The mean time for resolution of the elevations of AST and ALT was 2.5 days (95% CI = 1.8-3.2) for AST and 2.8 days (95% CI = 2.0 -3.6) for ALT. Conclusions:Significant elevations in AST and ALT occur when tumor involving the liver is ablated in women undergoing debulking for ovarian cancer. This elevation does not appear to increase operative blood loss or need for transfusion.
Perioperative positioning management in gynecologic cancer surgery: A national NOGGO-AGO intergroup survey.
Authors: Sporkmann Mareike , Wagner Jenny Katharina , Richter Rolf , Burges Alexander , Schmalfeldt Barbara , Veldink Hendrik , Schrettenbrunner Irmela , Pietzner Klaus , Sehouli Jalid 
Published: September 2018

e17046 Background: Perioperative positioning injuries occur in approximately 4% of all medical complications. The aim of the present survey was the analysis of positioning-management in gynecologic-oncological surgery, the process- and structure-reliability and the implementation of current guidelines into daily clinical practice. Methods: A multiple-choice anonymous questionnaire about the perioperative positioning management in gynecologic oncology was sent to all gynecological departments in Germany. Sixty questions were divided into five different parts: 1) descriptive information about the department, 2) focus on the pre- and 3) postoperative management, 4) on the quality management, and 5) information regarding the management of positioning in the operation room based on two fictional case examples in gynecologic oncology procedures. Results: 184 of 633 departments participated in the survey between June and September 2016. Complications related to intraoperative positioning occurred in 48.4% of all participating departments, independent from department size. Knowledge of the current guideline on positioning did not impact the incidence of complications. The positioning of the patient was mentioned in the team-time-out procedure in 66.1% of the participating departments. No difference was found between high-volume and low-volume gynecologic oncologic operative departments with regard to the use of supportive tools such as anti-thrombotic leg pumps. The vast majority with 92.7% included information of positioning injuries into the written informed consent. Knowledge of the guideline or a previous legal dispute did not influence the willingness to inform about possible positioning-related complications. Conclusions: Our survey shows, that the awareness of perioperative positioning management in gynecologic cancer surgery is high throughout all sizes departments in Germany. Almost half of all 184 participating departments report positioning-related complications in the previous 12 months, stressing the importance of this often underrated topic.
Reactive oxygen species in patients with ovarian adenocarcinoma treated with platinum based chemotherapy.
Authors: Rodica Maricela Anghel , Gales Laurentia , Gruia Maria Iuliana , Trifanescu Raluca Alexandra , Curea Fabiana , Botnariuc Inga , Trifanescu Oana 
Published: September 2018

e17047 Background: Ovarian adenocarcinoma (OA) is the most lethal of gynecologic tumors because women generally present with advanced stage disease. Platinum-based chemotherapy plays a pivotal role in OA treatment. The aim of the study was to assess the role of oxygen species in patients with OA and the effects of platinum based chemotherapy on blood redox status. Methods: Twenty three patients with advanced stage IIIC or IV OA who underwent platinum salts chemotherapy were included. Blood sample were collected before treatment, at 21 days (second cycle of chemotherapy) and at 42 days (3rd cycle) and at 63 day (4th cycle) with a platinum salt (cisplatin or carboplatin). Biochemical determination of oxidative stress was made by mesuring lipid peroxidation index (LPI), the enzymatic activity of ceruloplasmin and the thiol albumin groups. Results: Median age at diagnosis was 52 years, and 47.8% of patients presented with stage IIIC and 52.2% with stage IV. Nine patients received for the first time platinum based chemotherapy and 14 received multiple lines of chemotherapy. Response rate after 4 cycles were partial in 30%, stable disease in 57%, and progression disease in 13%. Mean value (± SD) of lipid peroxides was 6.81±1.μmol/100 ml (normal value 0-4), and of ceruloplasmin 156 ± 66 UI (normal value 80-120) which showed an increase of the final products of lipid peroxidation. Thiol mean value was 296±124 μmol/l (normal value 370- 450). The evolution of these reactive oxygen species were monitored during chemotherapy cycles. Decrease of the lipid peroxidation after 1st cycle was noticed, (7, 6.89, 5.87, 6.61), because platinum salt can bind peroxyde and this can be considered a marker of effectiveness of treatment.The thiol levels increased from one cycle to other (233, 311, 384, 393) showing that the cell is trying to contracarete the oxidative stress. Conclusions: Tumors produces reactive oxygen species in excess in patients with advanced OA. Platinum based chemotherapy in patients with OA induces radical formation and the dynamic of these markers may be used to monitor response to treatment.
Testing of BRCA 1/2 gene mutations in FFPE samples of patients with high-grade serous ovarian cancer and limits of its bioinformatic interpretation.
Authors: Janikova Katarina , Lasabova Zora , Grendar Marian , Farkasova Anna , Scheerova Karla , Slavik Pavol , Vanova Barbora , Zelinova Katarina , Jagelkova Marianna , Plank Lukas 
Published: September 2018

e17060 Background: BRCA1/2 mutations represent first genetically defined predictive markers for targeted therapy of patients with recurrent high-grade serous carcinoma (HGSC), therefore patients with HGSC should be tested for a germline and somatic BRCA mutation (g BRCAm and s BRCAm, resp.). In our study we analyzed possibilities and limits for determination of both origin and pathogenicity of mutations detected by HGSC biopsies analyses. Methods: We present data obtained by massive parallel sequencing on Miseq (Illumina). Library for sequencing was prepared by Somatic BRCA Tumor MASTR Plus kit (Multiplicom) from DNA isolated from HGSC FFPE tissue of 42 patients allowing simultaneous identification of g BRCAm and s BRCAm. For the pathogenicity evaluations we followed American College of Medical Genetics and Genomics (ACMG) criteria and used various bioinformatic tools. Results: All sequencing data were interpreted by SOPHIA DDM (Sophia Genetics) commercial tool. BRCA1/2 mutation was absent in 43% and present in 50% of patients, while 7% of cases had to be retested due to low coverage. Data of 28/42 patients were analyzed also by Ingenuity (Qiagen), the comparison of both the tools identified discrepant pathogenic determinationin 29% of them. The discrepancies in origin and pathogenicity of already detected mutations were found also by analyzing the data in other non-commercial databases (dbSNP, COSMIC, ClinVar, BIC, etc.). Conclusions: At least in a certain proportion of the cases, the data obtained by HGSC biopsy specimen mutational analyses and interpreted by accessible bioinformatic tools may lead to an equivocal assessment of both origin and pathogenicity of detected BRCA1/2 mutations. Other studies are necessary to eliminate the observed discrepancies.
VEGF-А in regulation of vascular endothelium functions and ascitic fluid production in ovarian cancer.
Authors: Moiseenko Tatiana , Frantsiyants Elena Mikhaylovna , Cheryarina Natalia D. , Pogorelova Yulia A. , Kozlova Larisa , Tkalya Lyudmila Dmitriyevna , Kravtsova Oksana E. , Adamyan Meri Viktorovich , Chalabova Tatiyana Georgievna , Kit Oleg I. 
Published: September 2018

e17067 Background: Our purpose was to study VEGF-A, VEGF-R1, VEGF-C and FGF21 in the blood serum (BS) and ascitic fluid (AF) in stage I-IV ovarian cancer. Methods: BS in serous cystadenocarcinoma (CAC, n=76) and cystadenoma (CA, n=47) was studied. Histological control was performed in all cases. The data were compared to BS in uterine myoma (UM, n=20) and in 36 healthy donors (N), all women aged 51.5±2.6 years. Native AF was studied in patients with CAC affecting one ovary without treatment (n=26, T3-4N0M0) and ovarian CA (n=12). Levels of VEGF-А, VEGF-R1, VEGF-С and FGF21 were measured by ELISA. Results: Levels of VEGF-A in CA BS exceeded N by 1.8, sVEGF-R1 – by 2, VEGF-C – by 1.7 and FGF21 – by 2.6 times. VEGF-A in T1N0M0 CAC exceeded N and CA by 2.9 and 1.6, in T2N0M0 – by 3.1 and 1.7, in T3NxM0 – by 5.5 and 3, in T4Nx-1M0 – by 5.8 and 3.1 times. sVEGF-R1 was similar in all CAC stages, on average twice higher than N, and similar to CA and UM. Differences were found between VEGF-А in CAC, CA and UM. sVEGF-R1 in all BS exceeded N (Р˂0.05 in all cases). VEGF-С in CA and UM BS exceeded N on average by 1.7 times, and in CAC it was significantly higher than in CA, UM and N. VEGF-С in BS in T1N0M0 was higher than in N and CA by 2.0 and 1.2, in T2N0M0 – by 2.6 and 1.6, in T3NxM0 – by 2.5 and 1.5, in T4Nx-1M0 – by 2.5 and 1.5 times, respectively. Differences in VEGF-С were found only in T1N0M0 and T2N0M0 by 1.3 times (Р˂0.05 in all cases). FGF21 in BS in UM and CA was similar, but differed from N by 2.6 times. FGF21 in all CAC stages exceeded BS and CA by 4 and 1.5 times. VEGF-А in CAC AF exceeded CA by 9.8, sVEGF-R1 – by 3.9; VEGF-C – by 1.6; FGF21 – by 1.7 times. VEGF-А, sVEGF-R1, FGF21 and VEGF-А/sVEGF-R1 in AF in UM and CA were similar to BS, and VEGF-С was lower than in BS by 1.7 times (Р˂0.05 in all cases). VEGF-А and sVEGF-R1 in BS in CAC were higher than in N by 2.9-5.8 and 2 times; in AF – higher than in UM by 9.9 and 4 times. VEGF-С in AF in CAC was lower than in BS on average by 1.6 times (Р˂0.05), and FGF21 did not differed in AF and BS. Conclusions: VEGF in SВ correlates with CAC stages distinguishing early and later ones. VEGF-А is higher than VEGF-C in BS and AF in all tumors. The VEGF family regulates functions of the endothelium of lymphatic and blood vasculature influencing oncogenesis and the occurrence of ascites.
The efficacy and safety of nedaplatin single therapy in 30 patients with platinum-resistant ovarian cancer.
Authors: Kasamatsu Yuka , Takekuma Munetaka , Kado Nobuhiro , Yoshioka Emi , Kuji Shiho , Tanaka Aki , Takahashi Nobutaka , Abe Masakazu , Hirashima Yasuyuki 
Published: September 2018

e17075 Background: This study aimed to investigate the efficacy and safety of Nedaplatin single therapy for patients with platinum-resistant ovarian, tubal and primary peritoneal cancer after completing standard chemotherapy. Methods: From September 2002 to August 2016, 30 patients who were diagnosed with platinum-resistant ovarian cancer, were treated with Nedaplatin single therapy after completing all standard chemotherapy at our institution. Nedaplatin (80-100mg/m2) was adiministered intravenously on day 1 of a 28 day cycle. We retrospectively investigated the response rate, toxicities, and survival based on the use of Nedaplatin single therapy. Results: The median age was 58.5 years (23-76). The median number of prior chemotherapy regimen was 3 (1-7). The median platinum-free interval between the final use of platinum analogues and starting Nedaplatin single therapy was 9.4 months (0.9-54.9). Among 22 patients who had measurable disease, 8 (36.4%) responded partially to Nedaplatin single therapy. Seven patients (23.3%) experienced hematological toxicities of Grade 3/4. Six patients (20.0%) experienced non-hematological toxicities Grade 2. No treatment-related death occurred. The median progression-free survival was 3.2 months (0-23.3), and over all survival was 9.2 months (1.1-56.4) after treatment with Nedaplatin single therapy. Age (<70 years, p=0.017) and platinum-free interval (<6 months, p=0.013) were the prognosis factors for survival in univariate analyses. Conclusions: Nedaplatin single therapy seemed to be an effective and safe chemotherapy regimen for platinum-resistant ovarian cancer after completing standard chemotherapy.
The activity of the conjugated antimetabolite 5-FdU-ECyd against platinum-resistant ovarian cancer.
Authors: Wimberger Pauline , Klink Barbara , Gruetzmann Konrad , Puppe Julian , Klotz Daniel , Schroeck Evelin , Kuhlmann Jan Dominik , Schott Sarah 
Published: September 2018

e17077 Background: Primary or secondary resistance to platinum-based chemotherapy is an important clinical challenge in the treatment of ovarian cancer (OC) and limits survival. Therefore, the development of innovative drugs against platinum resistance is urgently needed. Our therapeutic concept is based on the conjugation of two chemotherapeutic compounds to a monotherapeutic pro-drug, which is taken up by cancer cells and is subsequently cleaved into several active cytostatic metabolites. Our in vitro study evaluates the effects of the conjugated antimetabolite 5-FdU-ECyd, consisting of 2-deoxy-5-fluorouridine (5-FdU) and ethynylcytidine (ECyd), on platinum-resistant OC cells. Methods: In vitro assays and RNA-Seq (Illumina) were applied for characterization of 5-FdU-ECyd treated platinum-sensitive A2780 and isogenic platinum-resistant A2780cis as well as independent platinum-resistant Skov-3-IP OC cells. Results: Nano molar 5-FdU-ECyd concentrations induced a rapid dose-dependent decline of cell viability in platinum-sensitive and platinum-resistant OC cells. The cytotoxicity of 5-FdU-ECyd was accompanied by the formation of DNA double strand breaks and by the induction of apoptosis, indicated by a strong increase of pro-apoptotic molecular markers (caspase-3/7 activation, PARP-cleavage). Moreover, 5-FdU-ECyd efficiently decreased cell migration of platinum-resistant OC cells and inhibited other tumor-associated cellular functions, such as clonogenic or spheroidal growth. Transcriptome analysis indicated that, independently of platinum-resistance status, 5-FdU-ECyd influences distinct cellular pathways, involved in cell cycle regulation, apoptosis, DNA-damage response and RNA/pyrimidine metabolism. Combination treatment of 5-FdU-ECyd and platin did not show a synergistic cellular response, suggesting the potential use of 5-FdU-ECyd as a monotherapeutic agent. Conclusions: Our data provide a rationale to characterize the effect of 5-FdU-ECyd in a pre-clinical in vivo setting. We hypothesize that this conjugate is a promising therapeutic option for OC patients with resistance to conventional platinum-based chemotherapy.
Synthetic lethality interaction between aurora kinases and CHEK1 inhibitors in ovarian cancer.
Authors: Alcaraz-Sanabria Ana Lucía , Nieto-Jimenez Cristina , Corrales-Sanchez Veronica , Serrano-Oviedo Leticia , Serrano-Heras Gemma , Pretel Fernando Andrés , Montero Juan Carlos , Burgos Miguel , Llopis Juan , Galan-Moya Eva María , Amir Eitan , Pandiella Atanasio , Ocana Alberto 
Published: September 2018

e17089 Background: Ovarian cancer is characterized by frequent mutations at TP53. These tumors also harbor germline mutations at homologous recombination repair (HR) genes, so they rely on DNA-damage checkpoint proteins, like the Checkpoint kinase 1 (CHEK1) to induce G2 arrest. In our study, by using an in silico approach, we identified a synthetic lethality interaction between CHEK1 inhibitors and mitotic Aurora Kinase A and B (AURKA/B) inhibitors. Methods: Gene expression analyses were used for the identification of relevant biological functions. OVCAR3, OVCAR8, IGROV1 and SKOV3 were used for proliferation studies. Alisertib was tested as AURKA/B inhibitor and LY2603618 as CHEK1 inhibitor. Analyses of cell cycle and intracellular mediators were performed by flow cytometry and western-blot. Stem cell properties were evaluated with immunofluorescence. Results: Gene expression analyses followed by functional annotation identified cell cycle as a deregulated function. Identified druggable kinases within this function included AURKA/B, TTK kinase and CHEK1. CHEK1 and AURKA/B inhibitors showed a synergistic interaction in different cellular models. Combination of Alisertib and LY2603618 triggered apoptosis, reduced the stem cell population and increased the effect of taxanes and platinum compounds. AURKA and CHEK1 were amplified in 8.7% and 3.9% of ovarian cancers, respectively. Expression of these genes was linked with detrimental clinical outcome. Conclusions: Amplification of AURKA and CHEK1 was observed in more than 12% of ovarian tumors. Our data describes a synthetic lethality interaction between CHEK1 and AURKA/B inhibitors with potential translation to the clinic.
Clinicopathologic characteristics of endometrial carcinoma metastatic to the ovary compared to endometrial carcinoma with synchronous ovarian carcinoma.
Authors: Rodriguez Gomez Hidalgo Natalia , Soslow Robert A. , Weigelt Britta , Sioulas Vasileios , Aloisi Alessia , Abu-Rustum Nadeem , Mueller Jennifer Jean , Makker Vicky , Leitao Mario M. 
Published: September 2018

e17105 Background: According to recent reports, sporadic synchronous endometrial and ovarian cancers (SEOCs) of endometrioid histology may be clonally related. We sought to characterize the clinicopathologic characteristics and outcomes of patients with SEOC compared to those with endometrial carcinoma felt to have metastasis to the ovaries. Methods: All patients with endometrial cancer who underwent primary surgery at our institution from 06/1993- 09/2014 were identified. We included cases with carcinoma in the endometrium and ovary. Pathology reports were reviewed to determine the pathologist’s assessment of whether the ovarian carcinomas were likely synchronous or metastatic. Patients with stage IV endometrial carcinoma, irrespective of presence of ovarian disease, were excluded. Appropriate statistical tests were performed. Results: We identified 76 eligible cases; 19 were deemed SEOCs and 57 endometrial carcinoma with ovarian metastasis (ECOM). Median age was 52 years (range, 32-71) and 63 years (range, 43-89), respectively (p = 0.4). Non-endometrioid histology was observed in 21% of SEOCs compared with 58% of ECOMs (p = 0.006). There was no myoinvasion in 32% of SEOCs compared with 9% of ECOMs (p = 0.01). Endometriosis was noted in 58% of SEOCs compared with 4% of ECOMs (p < 0.0001). The median follow-up time was 44.2 months (range, 0.4-201.4) for the entire cohort. The 4-year progression-free survival (PFS) rates were 82% (SE+/-9.5) for SEOCs and 51.6% (SE+/- 7) for ECOMs (p = 0.06). The 4-year overall survival (OS) rates were 94.7% (SE+/-5.1) for SEOCs and 69.8% (SE+/-6.2) for ECOMs (p = 0.046). The 4-year PFS rates for cases of endometrioid histology alone were 84% (SE+/-10.6) for SEOCs and 77.8% (SE+/-8.87) for ECOMs (p = 0.97). The 4-year OS rates for cases of endometrioid histology alone were 93.3% (SE+/-8.4) and 81.9% (SE+/-8.2), respectively (p = 0.3). Conclusions: SEOC was associated with more favorable endometrial factors and with the presence of endometriosis, consistent with the notion that these are likely dissemination by retrograde flux. SEOC was associated with better survival outcomes but not when analyzing endometrioid histology alone.