scholarly journals Transcription factors HIF-1 α and NF- kB of tumor tissue and ascites cells in advanced ovarian cancer

2020 ◽  
pp. 30-36
Author(s):  
Т.В. Абакумова ◽  
С.О. Генинг ◽  
Д.Р. Долгова ◽  
И.И. Антонеева ◽  
Т.П. Генинг ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Transcription Factors ◽  
Ascitic Fluid ◽  
Tumor Tissue ◽  
Ovarian Tissue ◽  
Advanced Ovarian Cancer ◽  
Strong Positive Correlation ◽  
Tumor Spread ◽  
Normal Ovarian Tissue ◽  
Study Results

Введение. Транскрипционный фактор NF-kB относят к эндогенным промоторам, вовлечённым в опухоль-индуцированное воспаление связанное с раком, который может быть активирован в ответ на гипоксию как и HIF-1α. При этом между системами NF-kB и HIF-1α могут существовать взаимосвязии компенсаторные пути. Цель исследования - изучение уровня экспрессии транскрипционных факторов HIF-1α и NF-kB в ткани первичной опухоли и опухолевых клетках асцитической жидкости и их корреляции с чувствительностью к платиносодержащей химиотерапии у больных распространённым раком яичников. Методика. У 20 больных с впервые диагностированным асцитным серозным раком яичников стадии Т3NX-1M0 и Т3NX-1M1 сразу после верификации диагноза получали асцитическую жидкость и выделяли эпителиальные клетки, а также забирали интраоперационно опухолевую и гистологически неизмененную ткань яичника, в которых оценивали уровень HIF-1α и NF-kB методом иммуноферментного анализа (eBioscience, США и Cloud-CloneCorp., США). Ядерные экстракты для определения содержания HIF-1α и NF-kB готовили в соответствии с инструкцией изготовителя. В зависимости от распространенности опухолевого процесса определяли экспрессию транскрипционных факторов, их корреляцию, а также прогностическую значимость в оценке безрецидивной выживаемости при раке яичников. Результаты. Корреляционные исследования показали статистически значимое увеличение (в 12 раз) содержания HIF-1α в опухолевой ткани рака яичников по сравнению с гистологически неизмененной тканью, в асцитической жидкости - в 3,1 раза; уровень NF-kB в опухолевой ткани значимо возрастал в 6,5 раза, в асцитической жидкости - в 2,2 раза. В гистологически неизмененной ткани яичников, у пациенток стадии Т3NX-1M1 по сравнению с материалом от больных стадии Т3NX-1M0 экспрессия обоих факторов была снижена. Корреляционные связи между содержанием HIF-1α и NF-kB как в опухолевой так и в гистологически неизмененной ткани были положительными сильными у пациентов на стадии Т3NX-1M0, и в клетках асцитической жидкости на стадии Т3NX-1M1.Установлено, что высокие уровни экспрессии в ткани опухоли HIF-1α и NF-kB резко сокращают длительность безрецидивного периода. Заключение. Полученные данные позволяют предполагать активацию основных сигнальных путей, обеспечивающих ассоциированные с опухолью воспалительные реакции при раке яичников стадии Т3NX-1M1 . Introduction. NF-kB belongs to endogenous promoters involved in tumor-associated inflammation. Like HIF-1α, NF-kB can also be activated in response to hypoxia. In this case, cross-talks and compensatory pathways can link the NF-kB and HIF-1α systems. The aim of this study was to evaluate the expression of transcription factors HIF-1α and NF-kB in primary tumor tissue and ascites tumor cells and their correlation with sensitivity to platinum-containing chemotherapy (CT) in patients with advanced ovarian cancer (OC). Methods. Samples of ascitic fluid were obtained from 20 patients with first diagnosed and verified stage T3NX-1M0 and T3NX-1M1 ascitic serous OC immediately after diagnosis, and epithelial cells were isolated from the ascitic fluid. Samples of tumor tissue and histologically normal ovarian tissue were also obtained from patients intraoperatively. Contents of HIF-1α and NF-kB were measured using enzyme immunoassay (eBioscience, USA and Cloud-Clone Corp., USA) in all samples. Nuclear extracts for measuring HIF-1α and NF-kB were prepared according to the manufacturer’s instructions. Expression of transcription factors, their correlation, and prognostic significance for relapse-free survival were determined depending on the tumor spread. Results. The content of HIF-1α was 12 times higher in the ovarian tumor tissue (p <0.05) and 3.1 times higher in ascitic fluid (p <0.05) than in histologically normal tissue; the content of NF-kB was increased 6.5 times in the tumor tissue (p ≤ 0.05) and 2.2 times in ascitic fluid (p ≤0.05). The expression of both factors was reduced in histologically normal ovarian tissue from patients with the T3NX-1M1 stage compared to patients with the T3NX-1M0 stage. A strong positive correlation was observed for contents of HIF-1α and NF-kB in both tumor and histologically unchanged tissue from patients with the T3NX-1M0 stage and in ascites cells from patients with the T3NX-1M1 stage. It was established that high levels of HIF-1α and NF-kB expression in tumor tissue dramatically reduced duration of the relapse-free period. Conclusion. The study results suggest activation of major signaling pathways for tumor-associated inflammatory reactions in T3NX-1M0 stage OC.

Phenotypic characteristics of mononuclear cells in human ovarian tumors — with special reference to cystic and ascitic fluid

1994 ◽  
Vol 4 (5) ◽  
pp. 298-305 ◽  
Author(s):  
S. Kullander ◽  
A. Rausing
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Ascitic Fluid ◽  
Mononuclear Cells ◽  
Ovarian Tissue ◽  
Total Cell ◽  
Ovarian Tumors ◽  
Cystic Fluid ◽  
Cell Counts ◽  
Normal Ovarian Tissue

The occurrence of mononuclear cells and their cell-surface phenotype was studied in cryo- and paraffin sections in 26 untreated ovarian tumors and in normal ovarian tissue. T cells (positive for CD4 or CD8 markers) were sparsely represented in all sections of normal ovarian tissue and benign ovarian tumors, and in most ovarian cancer sections. B cells were found in three malignant tumors, CD57-positive (natural killer) cells in two, and CD25 (interleukin-2 receptor)-positive cells in one. Macrophages occurred sparsely both in normal ovarian tissue and in benign and malignant ovarian tumors. One endometrioid ovarian cancer, however, manifested rich infiltration of T cells (predominantly positive for CD8 marker). Cystic fluid from malignancies manifested higher prostaglandin concentrations and total cell counts than did benign cystic fluid, but sparse lymphocytes as a rule (5–10% of the total cell count). As compared to cystic fluid, ascitic fluid had higher concentrations both of prostaglandins and cells, with up to 25% lymphocytes in connection with malignancies. Immunogenic activity thus would appear to be weak in ovarian cancer. The harvest of tumor-infiltrating lymphocytes (TIL) from cystic fluid in ovarian cancers is moderate, compared to that of tumor-associated lymphocytes (TAL) from corresponding ascitic fluid samples.

Ovarian Cancer: Differentially Expressed microRNAs in Tumor Tissue and Cell-Free Ascitic Fluid as Potential Novel Biomarkers

2019 ◽  
Vol 37 (9) ◽  
pp. 440-452 ◽  
Author(s):  
Luděk Záveský ◽  
Eva Jandáková ◽  
Vít Weinberger ◽  
Luboš Minář ◽  
Veronika Hanzíková ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ascitic Fluid ◽  
Tumor Tissue ◽  
Differentially Expressed ◽  
Novel Biomarkers

scholarly journals Coincidence of Intra-Abdominal Splenosis in a Patient with Advanced Ovarian Cancer: Case Report and Review of the Literature

2021 ◽  
Vol 07 (02) ◽  
pp. e116-e120
Author(s):  
Tatjana Braun ◽  
Amelie De Gregorio ◽  
Lisa Baumann ◽  
Jochen Steinacker ◽  
Wolfgang Janni ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Case Report ◽  
Diagnostic Imaging ◽  
Medical History ◽  
Rare Disease ◽  
Metastatic Cancer ◽  
Abdominal Cavity ◽  
Advanced Ovarian Cancer ◽  
Splenic Tissue ◽  
Tumor Spread

AbstractSplenosis is a rare disease, which is often discovered incidentally years after surgical procedures on the spleen or traumatic splenic lesions. Through injury of the splenic capsule, splenic cells are able to spread and autoimplant in a fashion similar to the process of metastatic cancer. Here we present the case of a 62-year-old female patient with a palpable tumor of the lower abdomen. Her medical history was unremarkable, except for splenectomy after traumatic splenic lesion in her childhood. Clinical examination and diagnostic imaging raised the suspicion of advanced ovarian cancer, which was further substantiated by the typical presentation of adnexal masses and disseminated peritoneal metastases during the following staging laparotomy. Surprisingly, we also found peritoneal implants macroscopically similar to splenic tissue. Microscopic examination of tissue specimens by intrasurgical frozen section confirmed the diagnosis of intra-abdominal splenosis. The patient then underwent cytoreductive surgery with complete resection of all cancer manifestations, sparing the remaining foci of splenosis to avoid further morbidity. This case demonstrates the rare coincidence of intra-abdominal carcinoma and splenosis, which could lead to intraoperative difficulties by misinterpreting benign splenic tissue. Therefore, splenosis should be considered in patients with medical history of splenic lesions and further diagnostic imaging like Tc-99m-tagged heat-damaged RBC scan could be used for presurgical distinguishing between tumor spread in the abdominal cavity and disseminated splenosis. The presented case report should not only raise awareness for the rare disease splenosis, but also emphasize the need to consider the possibility of simultaneous incidence of benign and malignant intra-abdominal lesions, as to our knowledge this is the first published case of simultaneous peritoneal carcinomatosis and splenosis.

TUMOR-ASSOCIATED FIBRINOLYSIS IN OVARIAN CARCINOMA - HPLC AND N-TERMINAL AMINO ACID ANALYSIS REVEAL THE PATHWAY OF DEGRADATION OF CROSSLINKED FIBRIN

1987 ◽  
Author(s):  
O Wilhelm ◽  
A Henschen ◽  
R Hafter ◽  
H Graeff
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Ascitic Fluid ◽  
High Performance ◽  
Degradation Products ◽  
Gel Filtration ◽  
Advanced Ovarian Cancer ◽  
Reversed Phase ◽  
Fibrin Degradation Products ◽  
Sds Page

Crosslinked fibrin has been demonstrated by immunohistochemi-cal tests to occur around tumor plugs, on the surface and in the stroma of the tumor in ovarian cancer. High levels of D-Dimer (200-800μg/ml), the characteristic terminal degradation product of crosslinked fibrin, are found in ascitic fluid of patients with advanced ovarian cancer. These findings suggest that fibrin polymerisation and degradation are related to and even may influence tumor growth. The kind of proteases which are responsible for degradation of crosslinked fibrin is, however, unknown.lt was the aim of this study to evaluate whether plasmin and/or other proteases are involved in tumor-associated fibrinolysis. Therefore the total high-molecular-weight fibrin degradation products in ascitic fluid were purified by protamine sulfate precipitation, gel filtration, immunoadsorption and compared with the components of plasmin-degraded crosslinked fibrin, i.e. DD,DY,YX,DXD and DXY, by direct SDS-PAGE in the absence of mercaptoethanol and after excision of the bands, mercaptolysis and re-electrophoresis. Pronounced similarity between the two sets of fragments was observed. For further information the fragments from the two sources were mercaptolysed and their polypeptide chain components separated by reversed-phase high-performance liquid chromatography, the components being identified by N-terminal sequence analysis and SDS-PAGE. Highly similar patterns were obtained and components corresponding to γ-γ ,γ-γ1, β, β2 and α1 could be recognized. The findings provide strong evidence for plasmin being the primary protease involved in ovarian carcinoma-related fibrinolysis, (supported by Deutsche Forschungsgemeinschaft.SFB 207, A2).

scholarly journals Mining expression and prognosis of FOLR1 in ovarian cancer by using Oncomine and Kaplan-Meier plotter

Pteridines ◽  
2019 ◽  
Vol 30 (1) ◽  
pp. 158-164
Author(s):  
Qingyuan Su ◽  
Qingyuan Lv ◽  
Ruijin Wu
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Ovarian Tumor ◽  
Ovarian Tissue ◽  
Progression Free Survival ◽  
Free Survival ◽  
Normal Ovarian Tissue ◽  
Oncomine Database ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Abstract Objective: To further explore folate receptor 1 (FOLR1) gene expression in ovarian cancer and its association with patients’ prognosis by deep mining the Oncomine and Kaplan-Meier plotter databases. Methods: FOLR1 mRNA expression data of ovarian cancer were retrieved from the Oncomine database and further analyzed by comparing tumor to healthy tissue. The prognostic value of FOLR1 in ovarian cancer was analyzed by Kaplan-Meier Plotter, an online survival analysis database. Results A total of 439 studies were included in the Oncomine database in multiple types of cancers. Of the 439 studies, there were 54 with statistical differences for the expression of FOLR1, 19 with increased expression of FOLR1 and 35 with decreased expression comparing ovarian cancer to normal ovary tissue. After searching the Oncomine database, six datasets were discovered comparing the mRNA expression in ovarian tumor to healthy tissue. FOLR1 mRNA expression in ovarian tumor was significantly higher than that of normal ovarian tissue (all p<0.05). The Kaplan-Meier Plotter database analyzed the correlation between FOLR1 expression and ovarian cancer patient’s prognosis. A significant difference of progression-free survival between FOLR1 high and low expressing groups was found in ovarian cancer patients (HR=1.14, 95%CI: 1.00-1.29, p=0.043). However, the overall survival was not statistically different between high and low FOLR1 expressing patients (HR=0.95, 95%CI: 0.84-1.09, p=0.48). Conclusion FOLR1 mRNA was found to be highly expressed in ovarian tumor compared to normal ovarian tissue. Elevated FOLR1 mRNA expression was associated with the poor progression-free survival.

scholarly journals Clinical and Laboratory Characteristics of Patients with Peritoneal Tuberculosis Mimicking Advanced Ovarian Cancer

2021 ◽  
Vol 10 (02) ◽  
pp. 102-106
Author(s):  
Amita Maheshwari ◽  
Sudeep Gupta ◽  
Shweta Rai ◽  
Bharat Rekhi ◽  
Rohini Kelkar ◽  
...  
Keyword(s):  
Ascitic Fluid ◽  
Advanced Ovarian Cancer ◽  
Ca 125 ◽  
Cancer Center ◽  
Peritoneal Tuberculosis ◽  
Surgical Biopsy ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Study Results ◽  
Abdominal Malignancy

Abstract Objectives Peritoneal tuberculosis can mimic advanced abdominal malignancy. We describe clinical and laboratory characteristics in a series of female patients with peritoneal tuberculosis who were referred to a tertiary cancer center with a diagnosis of suspected advanced ovarian/primary peritoneal cancer. Materials and Methods Details of clinical features, laboratory results including serum tumor markers, radiological findings, and ascitic fluid evaluation were retrospectively collected from hospital records for patients diagnosed to have peritoneal tuberculosis and reported descriptively. Statistical Analysis Descriptive statistics was performed using SPSS Statistics for Windows software, version 20.0 (SPSS, Chicago, Illinois). Results Between January 2009 and December 2017, 120 patients of peritoneal tuberculosis with a median age 41 years (range, 15–79 years) were identified. Of these 112 (93.3%; 95% CI 88.9–97.8%) patients had ascites and 63 (52.5%; 95% CI 43.6–61.4%) had adnexal mass at presentation. Mean serum cancer antigen 125 (CA-125) level was 666.9 (range, 38–18,554) U/mL. Ascitic fluid was negative for malignant cells in all patients and lymphocyte rich exudate was seen in 103 (91.9%; 86.9–97.0%) patients. Ascitic fluid adenosine deaminase (ADA) level was more than 40 U/L in 107 (95.5%; 95% CI 91.7–99.4%). Ascitic fluid Ziel–Neelsen staining was positive in 4/62 (6.5%; 95% CI 0.3–12.6%) patients while ascitic fluid culture examination for mycobacterium tuberculosis was positive in 7/59 (11.9%; 95% CI 3.6–20.1%) patients. The diagnosis of tuberculosis was based on image-guided biopsy in 44 (36.7%) patients, surgical biopsy in 8 (6.7%) patients, and a combination of clinicoradiological and laboratory features in 68 (56.7%) patients. All patients received standard antitubercular treatment. Conclusions The study results suggest that peritoneal tuberculosis has clinical, radiological, and serological profile which may mimic advanced ovarian/primary peritoneal cancer. Peritoneal tuberculosis should be considered in the differential diagnosis of advanced abdominal malignancy.

scholarly journals Ascitis as a unique microenvironment of tumors in ovarian cancer: interaction with prognosis and chemoresistance

2019 ◽  
Vol 6 (2) ◽  
pp. 8-20
Author(s):  
A. B. Villert ◽  
L. A. Kolomiets ◽  
N. V. Yunusova
Keyword(s):  
Ovarian Cancer ◽  
Ascitic Fluid ◽  
Tumor Tissue ◽  
Molecular Genetic ◽  
Biomarker Detection ◽  
Ovarian Carcinomas ◽  
System Parameters ◽  
Igf System ◽  
Genetic Level ◽  
Igfbp 3

The severe heterogeneity of ovarian carcinomas on the molecular genetic level is associated with the absence of specific markers of chemoresistance. At the same time, ascites is an attractive biomarker detection fluid because it is easily obtained. The review is dedicated to the latest advances in the study of components characteristics of ascitic fluid in terms of their relationship with chemoresistance. Оwn data are submitted regarding the contents of the IFR system parameters (free IGFs, as well as IGFBP-3, IGFBP-4 and PAPP-A) in ascitic fluids and tumor tissue in disseminated ovarian cancer, which show the importance of their study. It is shown that the proteins level of the IGF system substantially depend on the volume of ascitic fluid. Studying the features of ascitic fluid in ovarian cancer is directly related to the prospect of new opportunities for disseminated ovarian cancer treatment.

scholarly journals Sensitivity of EGFR/HER-2 Positive Cells Isolated from Ascitic Fluid of Advanced Ovarian Cancer Patients to EGFR/HER-2 Inhibitors

2020 ◽  
Vol 10 (7) ◽  
pp. 2343
Author(s):  
Kenny Chitcholtan ◽  
Dianne Harker ◽  
Bryony Simcock ◽  
Peter Sykes
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Ascitic Fluid ◽  
Cancer Cell ◽  
Protein Level ◽  
Advanced Ovarian Cancer ◽  
Immunofluorescent Staining ◽  
Ovarian Cancer Cells ◽  
Her 2

Background: advanced ovarian cancer often presents with ascites. These ascites contain small clusters of cancer cells, which may contribute greatly to the metastatic potential of ovarian cancer in the peritoneal cavity. Therefore, understanding the unique protein expressions of this cell population will provide vital information for the development of tailored, targeted treatment. In this study, we isolate floating ovarian cancer cells from ovarian cancer patient ascitic fluid and use these cells to document that the expression of EGFR/HER-2 proteins may be essential for the growth and survival of these floating cancer cell clusters. Methods: ascitic fluid-derived cells were isolated from ascitic fluid by using Ficoll separation. Cells were cultured in a non-adherent condition for six days. The protein level of EGFR, HER-2, AKT, and ERK and their phosphorylation in ovarian cancer cell lines were determined by immunofluorescence. The immunofluorescent staining for proteins presented in ascitic fluid-derived cells determined the intensity profile of each protein using Carl Zeiss Blue software. Results: Isolated ovarian cancer cells from ascitic fluid have a measurable level of EGFR and HER-2 proteins. The inhibition of EGFR and EGFR/HER-2 positive cells with gefitinib and canertinib selectively disrupts cell viability and the protein level of EGFR, HER-2, AKT and ERK and their respective phosphorylation status. In addition, the dual EGFR/HER-2 inhibitor canertinib demonstrates greater anti-tumour effects than gefitinib in EGFR/HER-2 positive cells. Conclusion: These studies reveal an important role of multiple activation of receptor tyrosine kinases in floating ovarian cancer cells, as well as the importance of a dual EGFR/HER-2 inhibitor used as alternative adjuvant therapy in advanced ovarian cancer patients.

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