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 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.

Proteomics of the ascitic fluid for the differentiation of advanced ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15510-e15510
Author(s):  
Gururao Hariprasad ◽  
Roopa Hariprasad ◽  
Lalit Kumar ◽  
Amit Kaushik ◽  
Alagiri Srinivasan
Keyword(s):  
Ovarian Cancer ◽  
Ascitic Fluid ◽  
Predictive Value ◽  
Advanced Ovarian Cancer ◽  
The Body ◽  
Apolipoprotein A1 ◽  
Differentially Expressed ◽  
Ovarian Cancers ◽  
Potential Biomarker ◽  
Clinical Scenarios

e15510 Background: Ovarian cancers are classified as primary, if it arises in the ovary and secondary or metastatic, if the origin is from other parts of the body. The clinical manifestations of these cancers in the advanced stage are very similar making it difficult to distinguish clinically, hiostopathologically and radiologicaly. The therapeutics and management of the primary and secondary malignancies are completely different. While, the advanced primary malignancies are treated by cytoreduction followed by chemotherapy, the metastatic tumors are treated mainly with palliative chemotherapy. The prognosis is better for primary than secondary ovarian cancer making their diagnosis very crucial for patient care. Methods: 1D and 2D-gel based proteomic approaches were used to study the differentially expressed proteins in the ascitic fluid of patients (10 primary and 4 secondary) with advanced ovarian cancer. The relative ratios of the protein expression were estimated by densitometric analysis. The bands/spots with more than three fold difference were subjected to in-gel trypsin digestion and identified by mass spectrometric analysis. The differential expression of one of the proteins was further validated by western blot experiments and ELISA. Results: Programmed Cell Death 1-Ligand 2 and apolipoprotein A1 were seen to be up regulated in the advanced primary ovarian cancer while apolipoprotein A4, and chain L, humanized version of the anti-human fas antibody Hfe7a were seen to be up regulated in the metastatic variant. Validation for the expression of apolipoprotein A1 shows that a 61.8ng/ml cut off is ideal to differentiate the primary and secondary advanced ovarian cancers. The assay has 100% sensitivity, 75% specificity, positive predictive value of 90.9%, negative predictive value of 100%, accuracy of 92.85% and a pre-test odds positive of 2.5. Conclusions: Proteomics of ascitic fluid is useful for the differentiation of advanced ovarian cancers. There are proteins which are differentially expressed in the ascitic fluid of patients with primary and secondary ovarian cancer. Apolipoprotein A1 is a potential biomarker that can be used to differentiate the closely mimicking clinical scenarios of advanced ovarian cancer.

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.

scholarly journals Proteomic Profile Mapping and Differential Expression of Protein in Ovarian Cancer

2021 ◽  
Vol 50 (12) ◽  
pp. 3667-3681
Author(s):  
Ambreen Tauseef ◽  
Asima Karim ◽  
Gulfam Ahmad ◽  
Qurratulann Afza Gardner ◽  
Muhammad Waheed Akhtar
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Ovarian Tissue ◽  
Protein Profile ◽  
Protein Profiling ◽  
Differentially Expressed ◽  
P Value ◽  
Differentially Expressed Proteins ◽  
Tissue Samples ◽  
Novel Biomarkers

This study aimed to characterize differentially expressed proteins in malignant ovarian tissue to find out potential novel biomarkers in ovarian cancer (OC). We enrolled 20 ovarian cancer patients (40-65 years) and an equal number of age-matched healthy women to get malignant and healthy ovarian tissue samples for protein extraction and quantification after tissue lysis. The protein profile was analyzed using two-dimensional gel electrophoresis followed by MALDI-TOF mass spectrometry. Based on the information thus obtained, the proteins were identified using the relevant software and protein databank to analyze the malignant and non-malignant ovarian tissue samples (n = 20/group). In this proteomic analysis of the ovarian tissue, 112 proteins were detected. Based on a minimum of ≥ 1.5-fold expression difference (p-value ≤ 0.05; FDR ≤ 0.05 and PMF ≥ 79), 17 proteins were found to be upregulated while 27 were downregulated in the malignant ovarian tissue. Six of these proteins have not been previously reported in ovarian cancer. Out of these, three are upregulated while the other three are downregulated. The upregulated proteins are centrosomal protein of 290 kDa (Cep290), uncharacterized protein C1orf109 (C1orf109) and GTPase-activating Rap/Ran-GAP domain-like protein 3 (GARNL3), and the three downregulated proteins identified are actin-related protein 3 (ARP3), cytosolic carboxypeptidase 3 (AGBL3) and NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10 (NDUFA10). This proteomic mapping not only provides data on protein profiling of ovarian cancer in Pakistani population for the first time but also reports six novel differentially expressed proteins, which have not been previously reported in ovarian cancer patients. They may serve as potential novel biomarkers after further validation for early diagnosis and prognosis of ovarian cancer. It also provides additional data to improve existing knowledge of already reported protein ovarian cancer biomarkers.

Establishment of Primary Cell Culture From Ascitic Fluid and Solid Tumor Obtained From Epithelial Ovarian Carcinoma Patients

2017 ◽  
Vol 27 (9) ◽  
pp. 2000-2005 ◽  
Author(s):  
Rajarshi Kar ◽  
Diwesh Chawla ◽  
Bindiya Gupta ◽  
Mohit Mehndiratta ◽  
Neelam Wadhwa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Cancer Cells ◽  
Ascitic Fluid ◽  
Solid Tumor ◽  
Tumor Tissue ◽  
Primary Cultures ◽  
Epithelial Ovarian Carcinoma ◽  
Ovarian Cancer Cells ◽  
Solid Tumor Tissue

ObjectiveOvarian cancer is the seventh leading cause of cancer death worldwide. This is mainly due to late diagnosis and high rate of relapse and resistance following chemotherapy. In the present study, we describe simple and cost-effective method to establish primary culture from ascitic fluid and solid tumor obtained from epithelial ovarian carcinoma patient, which may provide a better tool for in vitro testing of drug sensitivity and designing individualized treatment protocol.MethodsComplete Dulbecco modified Eagle medium (DMEM) was prepared by supplementing DMEM with 10% fetal bovine serum and antibiotics (ciprofloxacin and amphotericin B). Establishment of primary culture of ovarian cancer cells from ascites fluid and solid tumor was done by using complete DMEM media.ResultsPrimary cultures of ovarian cancer cells were established from ascitic fluid and solid tumor tissue. Of the 7 ascitic fluid samples, we were able to establish 5 primary cultures of ovarian cancer cells. All the 7 samples were diagnosed as serous papillary adenocarcinoma. Some fibroblasts were also attached to culture flask on day 4; they were removed by exposing them to trypsin for a brief period. On day 7, grape-like clusters were visualized under inverted microscope. The cells became confluent on the 10th and 11th day and showed cobblestone appearance, which is a hallmark of ovarian cancer cells. Senescent irregularly shaped cells that have ceased dividing were seen after 8 to 10 passages.ConclusionThis study highlights the fact that establishing primary cultures from ascitic fluid or solid tumor tissue may help us to understand the molecular profile of the cancer cells, which allow us to select the best chemotherapeutic agent for ovarian cancer patients and thus take a step toward patient-tailored therapy so that patients are not exposed to drugs to which they are not likely to respond.

Clinical and Scintigraphic Findings in Radiation Myositis Complicating the Intraperitoneal Administration of 198Au

1965 ◽  
Vol 05 (02) ◽  
pp. 188-196
Author(s):  
J. Němec ◽  
J. Kubalt ◽  
S. Vohnout ◽  
J. Schubert ◽  
J. Sudek ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ascitic Fluid ◽  
Saline Solution ◽  
Intraperitoneal Administration ◽  
Clinical Findings ◽  
Safety Measures ◽  
Muscle Necrosis

SummaryPraeperitoneal administration of colloidal 198Au complicating the treatment of anascitic ovarian cancer is reported. Typical scintiscans and various clinical findings of muscle necrosis and radiation myositis are described. Administration of larger amount of saline solution preceding the radiogold instillation controlled by simultaneous scintiscanning are suggested as safety measures in patients when no ascitic fluid is present.

Calreticulin is Differentially Expressed in Invasive Ductal Carcinoma: A Comparative Study

2019 ◽  
Vol 16 (2) ◽  
pp. 148-155
Author(s):  
Asma Tariq ◽  
Rana Muhammad Mateen ◽  
Iram Fatima ◽  
Muhammad Waheed Akhtar
Keyword(s):  
Invasive Ductal Carcinoma ◽  
Tumor Tissue ◽  
Ductal Carcinoma ◽  
Tissue Level ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Two Dimensional Gel Electrophoresis ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Grade Ii

Objective: The aim of the present study was to build protein profiles of untreated breast cancer patients of invasive ductal carcinoma grade II at tissue level in Pakistani population and to compare 2-D profiles of breast tumor tissues with matched normal tissues in order to evaluate for variations of proteins among them. Materials & Methods: Breast tissue profiles were made after polytron tissue lysis and rehydrated proteins were further characterized by using two-dimensional gel electrophoresis. On the basis of isoelectric point (pI) and molecular weight, proteins were identified by online tool named Siena 2-D database and their identification was further confirmed by using MALDI-TOF. Results: Among identified spots, 10 proteins were found to be differentially expressed i.e.; COX5A, THIO, TCTP, HPT, SODC, PPIA, calreticulin (CRT), HBB, albumin and serotransferrin. For further investigation, CRT was selected. The level of CRT in tumors was found to be significantly higher than in normal group (p < 0.05). The increased expression of CRT level in tumor was statistically significant (p = 0.010) at a 95% confidence level (p < 0.05) as analyzed by Mann-Whitney. CRT was found distinctly expressed in high amount in tumor tissue as compared to their matched normal tissues. Conclusion: It has been concluded that CRT expression could discriminate between normal tissue and tumor tissue so it might serve as a possible candidate for future studies in cancer diagnostic markers.

scholarly journals The Assessment of IL-21 and IL-22 at the mRNA Level in Tumor Tissue and Protein Concentration in Serum and Peritoneal Fluid in Patients with Ovarian Cancer

2021 ◽  
Vol 10 (14) ◽  
pp. 3058
Author(s):  
Aleksandra Mielczarek-Palacz ◽  
Celina Kruszniewska-Rajs ◽  
Marta Smycz-Kubańska ◽  
Jarosław Strzelczyk ◽  
Wojciech Szanecki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Peritoneal Fluid ◽  
Tumor Tissue ◽  
Mrna Level ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
First Time ◽  
Ovarian Serous Cancer

The aim of the analysis was for the first time to assess the expression of genes encoding IL-21 and IL-22 at the mRNA level in ovarian tumor specimens and the concentration of these parameters in serum and peritoneal fluid in patients with ovarian serous cancer. The levels of IL-21 and IL-22 transcripts were evaluated with the use of the real-time RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proteins. Quantitative analysis of IL-21 gene mRNA in the tumor tissue showed the highest activity in the G1 degree of histopathological differentiation and was higher in G1 compared to the control group. The concentration of IL-21 and IL-22 in the serum and in the peritoneal fluid of women with ovarian cancer varied depending on the degree of histopathological differentiation of the cancer and showed statistical variability compared to controls. The conducted studies have shown that the local and systemic changes in the immune system involving IL-21 and IL-22 indicate the participation of these parameters in the pathogenesis of ovarian cancer, and modulation in the IL-21/IL-22 system may prove useful in the development of new diagnostic and therapeutic strategies used in patients, which require further research.

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