bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue factor pathway inhibitor II as a specific biomarker for pre-operative prediction of clear-cell carcinoma of the ovary.
Authors: Miyagi Etsuko , Arakawa Noriaki , Ruiz Yokota Naho , Yamanaka Takeharu , Sakamaki Kentaro , Miyagi Yohei , Yamaguchi Satoshi , Nagao Shoji , Yamada Yuki , Hirashima Yasuyuki , Kasamatsu Yuka , Kato Hisamori , Kitagawa Masakazu , Kobayashi Hiroshi 
Published: May 2020

e18077 Background: Tissue factor pathway inhibitor 2 (TFPI2) is a novel serum biomarker that discriminates ovarian clear cell carcinomas (CCC) from borderline ovarian tumors (BD) and non-CCC epithelial ovarian cancers (EOC). We examined the prediction performances of TFPI2, including high specificity, for preoperative diagnosis of CCC in multi-center settings. Methods: We collected serum samples obtained preoperatively from patients with ovarian masses who needed surgical treatment to confirm pathological diagnoses in five hospitals in Japan. The diagnostic powers of serum levels of TFPI2 (cutoff value 270 pg/mL) and CA125 (cutoff value 35 U/mL) to discriminate CCC from BD, non-CCC-EOC, and benign lesions were compared. Results: A total of 351 patients (77 ovarian benign lesions, 65 BD and 209 EOC including 69 CCC) were analyzed. Serum TFPI2 levels were significantly higher in CCC patients (mean±SD, 508.2±812.0 pg/mL) than in patients with benign lesions (154.7±46.5), BD (181±95.5) and non-CCC EOC (265.4±289.1). TFPI2 had a high diagnostic specificity to CCC (sensitivity and specificity: 43.5% and 79.5%, respectively). The sensitivity of TFPI2 was improved to 71.1% when combined with CA125, and it was increased in Stage II–IV CCC (66.7%) compared with Stage I CCC (33.3%). In patients with benign endometriotic cysts (BEM), no patient was positive for TFPI2 but 71.4% (15/21) were CA125 positive. TFPI2 showed good performance in discriminating Stage II–IV CCC from BD and non-CCC EOC patients (AUC 0.815 for TFPI2 versus 0.505 for CA125) or from BEM (AUC 0.957 for TFPI2 versus 0.748 for CA125). Conclusions: High specificity of TFPI2 for the preoperative detection of CCC was re-verified with the defined cutoff level of TFPI2 in practice. TFPI2 and CA125 may have a substantial contribution to the precise prediction of intractable CCC. [Table: see text]
Immunomodulator in combination treatment of patients with ovarian cancer and its influence on DNA cytometric and immunological parameters.
Authors: Ardzha Anna Yu. , Verenikina Ekaterina V. , Zlatnik Elena Yu. , Nikitina Vera P. , Zhenilo Oksana E. , Nikitin Ivan S. , Kit Oleg I. , Dzhenkova Elena A. 
Published: May 2020

e18079 Background: Immunotherapy in oncology has now proven effective, but standard approaches have not yet been defined. Ways to optimize and increase the effectiveness of treatment with immunomodulators, in particular interferon-gamma preparations, in such patients remain an urgent problem of gynecological oncology. The purpose of the study was to improve direct results of ovarian cancer treatment. Methods: The study included patients aged 50-77 years with inoperable ascitic ovarian cancer (verified by cytological examination of ascitic fluid), stage IIIC-IV, receiving neoadjuvant chemotherapy (CT) in combination with immunotherapy with interferon-gamma (IFNγ). Group I – 26 patients, CT with carboplatin (AUC-6), paclitaxel (175 mg/m2); group II – 22 patients, chemoimmunotherapy and intramuscular IFNγ (ingaron) - 500 000 IU on day 1, 1 million IU on days 2,3,5, a similar CT on day 4; group III – 24 patients, chemoimmunotherapy and intraperitoneal IFNγ (ingaron) - 500 000 IU on day 1, 1 million IU on days 2,3,5, a similar CT on day 4. Patients received on average 2-3 therapy cycles. Results: Progression was registered only in group I in 3.8%; complete response in patients without IFNγ – 7.8%, with intramuscular and intraperitoneal IFNγ – 27.3% and 37.5% (p≤0.05) respectively. Surgical treatment followed in all patients, with total surgeries in 87.5% of patients with intraperitoneal IFNγ. DNA cytometry showed the minimal number of aneuploid tumors in patients with intraperitoneal IFNγ (16.6%), while in patients without immunotherapy 38.4%. The DNA index statistically significantly decreased by 1.3 times in patients with intraperitoneal IFNγ compared with patients without IFNγ (1.11±0.01% vs. 1.4±0.05% respectively) (p≤0.05). Levels of CD3+CD4+ cells elevated by 1.2 times (from 36.2±1.6 to 44.9±3.78%, p≤0.05) in patients with intramuscular IFNγ; intraperitoneal IFNγ caused an increase in CD3+ lymphocytes by 1.3 times (from 62.1±2.8 to 77.9±2.94%, p < 0.05) and CD3+CD4+ by 1.4 times (from 36.2±1.6 to 50.6±5.9%, p≤0.05). Conclusions: Interferon-gamma (ingaron) in combination with CT improves direct results of the treatment; intraperitoneal injections of interferon-gamma demonstrated better outcomes and tolerance confirmed by immunological and DNA cytometric parameters.
Markers of a metastatic niche in the omentum in ovarian cancer.
Authors: Moiseenko Tatiana I. , Frantsiyants Elena M. , Kaplieva Irina V. , Bandovkina Valeria A. , Cheryarina Natalia D. , Menshenina Anna P. , Adamyan Meri L. , Verenikina Ekaterina V. , Yakubova Darya , Boyko Konstantin P. , Ilchenko Maria G. , Gurnak Viktor V. , Agarkova Elena I. , Chalabova Tatiana G. , Kit Oleg I. 
Published: May 2020

e18081 Background: Ovarian cancer spreads intraperitoneally due to the interaction of tumor cells and the omental mesothelium, creating a metastatic niche and supporting elements of cancer cell expansion such as adhesion, proliferation, migration, and neoangiogenesis. The purpose of the study was to analyze levels of VEGFA, IGF-I, IGF-II and TGFβ1 in omental tissues in ovarian cancer (OC). Methods: The main group included 23 patients with metastatic OC T3-4аN0-3M1; the comparison group – 21 patients with non-metastatic OC T3-4аN0-3M0; the control group – 19 non-cancer patients. Levels of VEGFA, IGF-I, IGF-II and TGFβ1 were measured by standard ELISA methods in tissues of primary tumors and the omentum. Results: Levels of growth factors in the comparison group were not elevated compared to control values. Growth factors in omental tissues in the main group were increased compared to control values: VEGFA – by 2.5 times, IGF-I – by 3.4 times, IGF-II – by 2.5 times, TGFβ1 - by 3.1 times. In the comparison group, the levels in omental tissues were lower than in the main group: VEGFA – by 1.7 times (p < 0.05), IGF-I – by 2.1 times, IGF-II – by 1.6 times (p < 0.05); TGFβ1 did not differ from the levels in the main group. Conclusions: Higher expression of VEGFА in the omentum with metastases can be considered a significant factor in the formation of signaling pathways between metastatic tumor cells and local non-cancer cells. IGF-I and IGF-II trigger the endothelial growth factor. The TGFβ1 activation in the omentum in metastatic ovarian cancer is necessary for the paracrine induction and transition of disseminated tumor and/or stem cells from the "sleeping" to the active state.
The regulation of RNA Polymerase II mediated transcription by Caspase-8 in ovarian cancer.
Authors: Becker Sven , Mandal Ranadip , Raab Monika , Sanhaji Mourad , Strebhardt Klaus 
Published: May 2020

e18082 Background: According to the WHO, in 2018, the number of new cases and mortality worldwide due to ovarian cancer, were 295,414 and 184,799, respectively, making it one of the most lethal gynaecological cancers in the world. The standard therapy of ovarian cancers is still comprehensive cytoreductive surgery followed by a combination of platinum-taxane based primary chemotherapy. Second line therapies include Carboplatin or Cisplatin in combination with Paclitaxel, PLD or Gemcitabine, with or without Bevacizumab. Unfortunately, late stage ovarian cancer cases are still incurable, however, several new drugs are under development or are undergoing clinical trials. At present, these new approaches can only stabilize the disease or delay its recurrence. Caspase-8, the predominant initiator of the extrinsic apoptotic pathway, also plays critical roles in a number of other non-apoptotic functions. It is also frequently down-regulated in ovarian cancer and we wanted to understand how this down-regulation could support the development of ovarian cancer. Methods: The analysis of the association between CASP8 expression and patient prognosis in ovarian cancer patients found that low CASP8 expression was significantly correlated with poor OS, with a median OS of 37.43 (low expression) and 49.97 (high expression) months, and higher clinical stages. CRISPR/Cas9 mediated CASP8 KO in multiple high- and low-grade ovarian cancer cell lines resulted in significant increases in their invasiveness. Results: Caspase-8 interactome analysis revealed that it can regulate the RNA Pol II mediated transcription, which was corroborated through multiple in vitro and ex vivo experiments. Global Transcriptomics and Proteomics analysis of the KO cells revealed significant upregulation of genes involved in metastasis, which was again verified in in vitro and ex vivo experiments. Additionally, the KO cells were significantly resistant towards standard chemotherapeutics like Carboplatin, a transcription inhibitor, either alone or in combination with Paclitaxel. Conclusions: Presently, we are working on orthotopic ovarian cancer mouse models to validate - the potential of Caspase-8 to regulate metastasis; and the targeting of RNA Pol II to sensitize them to standard chemotherapeutics. We are also developing organoid banks from patient derived ovarian cancer tissues, with low Caspase-8 expression, to validate the upregulation of genes identified in our ‘omics’ data and the potential of targeting them, along with RNA Pol II, to sensitize them to standard chemotherapeutics.
Adult ovarian granulosa cell tumor: Role of systemic chemotherapy and surgical treatment.
Authors: Beliaeva Anna , Bakhidze Elena 
Published: May 2020

e18083 Background: Granulosa cell tumor (GCT) are rare sex cord-stromal tumours. Their frequency is approximately 3% - 5% of all malignant ovarian tumors, and the incidence is from 0.6 to 2.1 cases per 100 000 women per year. According to the histological features, GCT are divided into two types: adult and juvenile. In the 2014 WHO histological classification, GCT were divided into borderline, which included the GCT of the juvenile type, and the malignant GCT of the adult type (AGCT). Despite the definition of AGCT not as borderline, but as low-grade malignant tumors, there are no specific recommendations for the surgical and drug treatment in such patients. Main method of treatment is surgical. Role of systemic treatment due to rarity of AGCT and late recurrence still has not determined. Methods: Data of 93 patients in our institution who were diagnosed with AGCT I-IV stage of the disease between 1980 and 2017 were evaluated. The data were obtained from the files of the patients, electronic database of the gynecologic oncology clinic, operation notes, and pathology records. Results: Stage of the disease, the spread of the tumor beyond the capsule and the number of mitoses of more than 10 significantly influenced the OS rates (p < 0.05). The average time before the onset of the first relapse in IA, IB stage was 134.5 months, in IC stage - 67.4 months, in II-IV stage - 34.3 months. Stage of the disease is an independent prognostic factor for the occurrence of a relapse of the disease. In stage I disease there was no influence of the volume of surgical treatment and adjuvant chemotherapy on DFS and the duration of disease-free period (p > 0.05). The duration of the non-progressive period was some, but not significantly more when performing optimal cytoreduction for the recurrence of the disease, and did not depend on the implementation regimen and adjuvant chemotherapy. Conclusions: There were not found significant difference in the overall and relapse-free survival of patients with ovarian AGCT, depending on the options of surgical and drug treatment they underwent. Studies showed that hormones play a critical role in the pathogenesis and treatment of GCT, especially in some ineffective cases for radiotherapy and chemotherapy. Additional multicenter randomized trials are needed to clarify the effectiveness of the various options for surgical and drug treatment of adult GCT patients.
Germline and somatic mutations in 25 hereditary breast and ovarian cancer related genes and platinum-based chemotherapy response among Chinese patients with epithelial ovarian cancer.
Authors: Li Lei , Wu Ming , Zhu Changbin , Shao Di , Liu Meng ,   Xiehe
Published: May 2020

e18088 Background: Insight on the germline and somatic mutation in BRCA1/2 was predictable on the sensitivity on platinum-based therapy. The therapeutic impact of mutations in other hereditary breast and ovarian cancer related genes is uncertain. Methods: We sought to investigate the germline and somatic deleterious mutations through all exons in 25 hereditary breast and ovarian cancer related genes in paired blood and frozen tumor samples from 235 Chinese women diagnosed with epithelial ovarian carcinomas. Results: Forty-seven subjects (24.6%) had a germline deleterious mutation, and 126 subjects (66%) had a somatic deleterious mutation. Thirty-four (17.8%) had both a germline and somatic mutation. Of the 203 germline and somatic deleterious mutations, 114 (56.2%) occurred in TP53, 41 (20.2%) in BRCA1, 11 (5.4%) in BRCA2 and 37 (23.6%) in 13 other genes: ATM, BARD1, BRIP1, CDH1, CHEK2, MLH1, MRE11A, MSH2, NF1, PALB2, PTEN, RAD51C and, STK11. In 235 patients, 215 (91.5%) and 20 (8.5%) cases were sensitive and resistant to the platinum-based chemotherapy. In the whole population, homologous recombination repair (HRR) mutations, non- homologous recombination repair(non-HRR) mutations, mismatch repair (MMR) mutations had no impact on the platinum-based chemotherapy response. No significant difference in platinum response were found in HRR, non-HRR and MRR mutation(P = 0.788). In 235 patients, ones with ATM (10), CHEK2(9), NF1(5), PALB2(8), PTEN (8) mutations were available for platinum response information; Among them, there were three patients with either ATM, CHEK2 or PALB2 mutation presented platinum resistance. Conclusions: Multi-gene panel testing of germline and somatic HBOC related gene mutations was feasible to characterize a comprehensive molecular profile of ovarian cancer and showed non-BRCA gene stratification potential value in predicting patient’s response for platinum-based chemotherapy.
Paraneoplastic ataxic syndrome with anti-Yo antibodies in breast and ovarian cancer: A retrospective analysis.
Authors: Puri Akshjot , Khan Usman , Niravath Polly Ann 
Published: May 2020

e18089 Background: Paraneoplastic cerebellar syndrome is a rare immunological reaction caused most commonly by Anti-Yo or Purkinje cell cytoplasmic antibody type 1(PCA1) to cerebellar degeneration protein 2(CDR2), found in the cerebellum and ectopically produced by tumor. Most cases are reported in women with HER2+ breast and ovarian cancers with underlying breast cancer patients having relatively better prognosis. Treatment initiation within one month of symptom onset has shown better outcomes. Methods: A retrospective analysis was conducted using a clinical database at a single institution and included 3 patients with a cancer diagnosis and ataxic symptoms diagnosed between 2016 and 2020. Data collection included age, gender, performance status, site of disease, pathology, diagnostic work up, treatment and overall survival (OS). Results: The study included 3 patients who presented with new onset ataxic symptoms with the median time of cancer diagnosis from onset of symptoms being 5 months (range 4-7). Median age was 62 years (range 59-83), all 3 patients were females and functionally independent before symptom onset. Out of 3 patients 2 had HER2+ breast cancer (one with IHC 3+ and one with equivocal IHC but 20 HER2 signals/nucleus) and the third had ovarian carcinoma. All 3 patients had stage IIIA disease as per AJCC 8th edition and presented with bilateral extremity weakness, ataxia, visual disturbances, vertigo and nausea/vomiting. Extensive neurological work up including MRI brain, CSF analysis, EEG were inconclusive except for high titres of anti- Yo antibodies in all patients. All patients were treated with cancer directed therapy and immunomodulation with plasma exchange, IVIG and steroids. The median OS being 22 months (range 12-28) with 2 patients with underlying breast cancer alive at the time of the analysis albeit there has been no neurological recovery, despite IVIG, steroids, and plasma exchange. Conclusions: The anti-Yo associated paraneoplastic ataxic syndrome most commonly associated with breast and pelvic tumors in women has a very poor prognosis despite anti-tumor and immunomodulating therapies, leaving most patients bed-ridden. The neurologic damage is irreparably incurred once the antibodies attack cerebellar cells. Thus, it is critical for clinicians to recognize the potential signs and symptoms as early as possible, so that treatment can be started, and long term symptoms are minimized. Further studies are needed to know the exact mechanism of this syndrome and provide evidence based treatment options.
National patterns and factors predicting employment disruption in women diagnosed with endometrial cancer.
Authors: Nitecki Roni , Fu Shuangshuang , Smith Benjamin D. , Meyer Larissa , Melamed Alexander , Rauh-Hain Jose Alejandro 
Published: May 2020

e18093 Background: Cancer patients are less likely to return to work after diagnosis. As endometrial cancer is highly curable, it is important to assess whether patients are able to resume work after treatment. We evaluated rates of return to work following endometrial cancer diagnosis and assessed factors associated with a disruption in employment. Methods: A cohort of patients aged 18-63 years who were diagnosed (2010-2015) with endometrial cancer and underwent surgical staging were identified in Truven Marketscan, an insurance claims database of commercially insured patients in the United States. All patients who were working full or part-time when diagnosed were included, and all employment changes during the year following diagnosis were identified. Treatment information, including use of chemotherapy and radiation, and complications of treatment were identified and collected using Common Procedural Terminology codes, and International Statistical Classification of Diseases codes. Univariable analysis and multivariable logistic regression were used to evaluate the impact of treatment and demographic variables on change in employment status. Results: A total of 3547 women with endometrial cancer who held a full-time or part-time job 3 months prior to diagnosis were identified. The median age at diagnosis was 55 years, and the majority of patients (82%) had a Charlson comorbidity index of 0. While most women continued to work following diagnosis, 21% (736) experienced a disruption in employment. The majority (96.7%) held a full-time job prior to going on long-term disability, retirement, or stopping to work. In univariable analysis, chemotherapy recipients were 40% more likely to experience a disruption in employment (Odds ratio (OR) = 1.5, 95% confidence Interval (CI) 1.15-2.11), whereas radiation therapy did not influence employment (OR 1.3, 95% CI 0.99-1.61). In multivariable analysis including age, region of residence, Charlson comorbidity, radiation, chemotherapy, insurance plan and presence of surgical complications, receipt of chemotherapy remained a significant predictor of employment disruption (OR 1.46, p = 0.0257). Conclusions: Twenty-one percent of employed, insured women experienced a change in employment following diagnosis of endometrial cancer, an often-curable disease. Chemotherapy was a significant predictor of employment disruption. This is important to consider in development of interventions to maximize functional recovery following treatment for endometrial cancer.
Diagnosis and treatment of uterine carcinosarcoma.
Authors: Beliaeva Anna , Bakhidze Elena 
Published: May 2020

e18111 Background: Uterine carcinosarcoma (UCS) is rare and highly aggressive malignant tumor belonging to mixed epithelial and mesenchymal tumors and classified as high-grade endometrial carcinoma. UCS is more prone to metastasis, especially in the lymph nodes, and 35% of the diagnostics show advanced process and worse treatment results. High UCS aggressiveness, unsatisfactory treatment results and the lack of standard approaches to its treatment require more researches. Methods: Clinical and morphological data of 72 patients from N.N. Petrov National Medical Research Center of Oncology treated from 2004 to 2014 were analysed. 28 patients were included with the UCS I – III stages based on clinical and morphological data. The average age of the patients was 61.5 years (43 to 82). Results: 15 patients had stage I (53.6%), 3 - stage II (10.7%), 10 – stage III (35.7%) with ovarian metastases 14.3% and omental - 18.2%. 5 patients received only surgical treatment; 21 received combined treatment, including surgery and radiation therapy (RT). Postoperative remote RT in combination with brachytherapy was applied in 18 patients, only brachytherapy - 5. Chemotherapy (CT) was used in 6 patients. Metastatic lesion of the iliac lymph was morphologically proven in 6 of 18 patients (31.6%). No correlation between frequency of regional metastasis and depth of tumor invasion to the myometrium was found. Overall survival was 52%, relapse-free - 32%, for stage I – II it reached 72.2%. Five-year survival for stage III was 44.4%. Recurrence rate after total hysterectomy with pelvic lymphadenectomy was 2 times lower compared to that without lymphadenectomy (30 and 62.5%, respectively). The relapse rate in patients with UCS I – II stages after surgical treatment without adjuvant RT reached 33.3%, with brachytherapy - 40%, with remote RT in combination with brachytherapy - 20%. Systemic treatment was applied to 6 patients, 2 of them did not undergo RT (relapses in these 2 patients were noted during the first year of observation). Conclusions: The overall 5-year survival and relapse-free survival of patients with UCS I – III stages is quite low: about 50% and 30%, respectively. Optimal surgical staging (which involves performing pelvic lymphadenectomy) and the use of adjuvant RT, can reduce the frequency of relapses. The use of systemic CT as an adjunct to surgical and radiation treatment is justified for patients with UCS from the standpoint of the same frequency of both local relapses and distant metastases.