Stem-like tumor cells and proinflammatory cytokines in the ascitic fluid of ovarian cancer patients

2021 ◽  
Vol 66 (5) ◽  
pp. 297-303
Author(s):  
S. O. Gening ◽  
T. V. Abakumova ◽  
I. I. Antoneeva ◽  
A. A. Rizvanov ◽  
T. P. Gening ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Blood Serum ◽  
Tumor Cells ◽  
Ascitic Fluid ◽  
Early Stage ◽  
Abdominal Cavity ◽  
Disease Stage ◽  
Cell Populations ◽  
Benign Ovarian Tumors ◽  
Number Of Cells

Ovarian cancer (OC) is able to develop implantation metastases in the abdominal cavity. Ascites is potentially useful for evaluating cancer features. The aim of the study was to assess the content of stem-like tumor cells and inflammatory mediators in ascites of OC. The prospective study included 11 patients with primary OC having ascites, 8 patients with benign ovarian tumors having ascites and 22 healthy women. In ascitic fluid obtained by laparocentesis, the populations of tumor stem-like cells were determined on a Cytoflex S` flow cytometer (Beckman Coulter, USA) and CytExpert Software using monoclonal antibodies to CD45, CD44 and CD133. The cytokine profiles of ascitic fluid and blood serum (IL-1β, IL-18, IL-4, IL-10 and VEGF) were assessed by ELISA. Stem-like cells were found in all samples. 5 cell populations were evaluated. The number of cells expressing both markers: CD44 + and CD133+, was the lowest. The highest, about 32%, was the number of CD44+ cells. The number of cells CD45-CD44+CD133- in ascites strongly positively correlated with the content of IL-10 in ascites, and the numbers of CD45-CD133+ and CD45-CD44-CD133+ - with the level of VEGF in blood serum. No correlations were found between the numbers of stem-like cells and the disease stage or the level of CA125 in blood. The combination of IL-4 and IL-10 in ascites had the greatest significance in predicting the disease stage. These results suggest a relationship between the levels of VEGF, IL-10, and cancer stem cells in the OC ascites. Stem-like cells in OC ascites are heterogeneous and are present even at an early stage of the disease. It seems promising to study cell populations and cytokine profile of ascites together, to assess the biomarker potential of their combination.

scholarly journals 41P Stem-like tumour cell populations and cytokine profile of the ascitic fluid in ovarian cancer

2020 ◽  
Vol 31 ◽  
pp. S1229-S1230
Author(s):  
S. Gening ◽  
I. Antoneeva ◽  
T. Abakumova ◽  
A. Rizvanov ◽  
D. Gafurbaeva ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ascitic Fluid ◽  
Tumour Cell ◽  
Cytokine Profile ◽  
Cell Populations

Role of CD70 in pathogenesis of ovarian cancer cell metastasis

2018 ◽  
Vol 6 (4) ◽  
pp. 315-322
Author(s):  
Jack L. Pincheira ◽  
Maria Wiseman
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Abdominal Cavity ◽  
Activated T Cells ◽  
Cancer Society ◽  
Tissue Samples

American Cancer Society identifying ovarian carcinoma as the gynecologic malignancy with the highest case-to-fatality. Ovarian carcinoma metastasizes either by direct extension from the ovarian/fallopian tumor to neighboring organs (bladder/colon) or when cancer cells detach from the primary tumor. Exfoliated tumor cells are transported throughout the peritoneum by physiological peritoneal fluid and disseminate within the abdominal cavity. Extensive seeding of the peritoneal cavity by tumor cells is often associated with ascites, particularly in advanced, high-grade serous carcinomas. CD70 (encoded by the TNFSF7 gene) is a co-stimulatory factor present on B-cells, activated T-cells, and dendritic cells. CD70 is over expressed in tumor cells of various solid cancers including ovarian carcinoma, recently reported the role of CD70 expression as a predictive marker of resistance to chemotherapy in ovarian cancers. We evaluated the expression of CD70 level in the pathogenesis of metastasis ovarian cancer cell. Seventy five tissue samples from metastatic ovarian carcinoma were evaluated by quantitative real-time PCR for CD70 and statistical analyses were performed using the Mann-Whitney test. Further, humanized anti-CD70 antibodies were investigated in xenograft mice models of ovarian cancer. Increasing expression of CD70 level was associated with increased risks for disease progression (HR = 1.04; 95% CI, 1.03 to 1.14) and death (HR = 1.13; 95% CI, 1.09 to 1.2). expression of CD70 was associated with a worse PFS and OS compared with non- expression of CD70 carcinomas. Furthermore, humanized anti-CD70 antibodies have shown significant antitumor activity in preclinical xenograft models of ovarian cancer cell.

Metabolic Markers and HSP60 in Chemonaive Serous Solid Ovarian Cancer Versus Ascites

2014 ◽  
Vol 24 (8) ◽  
pp. 1389-1394 ◽  
Author(s):  
Elisabet Hjerpe ◽  
Suzanne Egyhazi Brage ◽  
Marianne Frostvik Stolt ◽  
Hemming Johansson ◽  
Maria Shoshan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Tumor Cells ◽  
Solid Tumor ◽  
Messenger Rna ◽  
Abdominal Cavity ◽  
Advanced Ovarian Cancer ◽  
Tumor Type ◽  
Heat Shock Protein 60 ◽  
Metabolic Markers

ObjectiveMetabolic pathway alterations in cancer are thought to be dependent upon tumor type–specific oncogenic activation and local nutrient and oxygen supply during disease progression. In serous ovarian cancer, the typical peritoneal spread of disease is caused by shedding of tumor cells into the abdominal cavity, often along with ascites formation. Not much is known about the metabolic features of these detached serous tumor cells. In this study, we investigate the messenger RNA (mRNA) expression of GAPDH (glycolytic glyceraldehyde 3-phosphate dehydrogenase) and PKM2 (pyruvate kinase isoform M2), ATP5B (mitochondrial β-F1-ATPase), and heat shock protein 60 in matched serous solid tumor and corresponding ascites.Materials/MethodsFresh samples from solid tumor and corresponding ascites were prospectively collected from 40 patients undergoing primary surgery for suspected advanced ovarian cancer. Of these, 25 met the study eligibility criteria, that is, stage IIC to IV disease of the serous (24) or endometrioid (1) subtype with solid and ascites specimens containing 50% or more tumor cells and with good quality and quantity mRNA yield. All but 2 patients (92%) had type II disease. GAPDH, PKM2, ATP5B, and HSP60 mRNA expressions were assessed by real-time polymerase chain reaction. For each marker, the mRNA expression in solid tumor was pairwise compared with the corresponding expression in ascites using the Wilcoxon matched pairs signed rank sum test.ResultsIn contrast to our hypothesis, the mRNA expression of analyzed metabolic markers and HSP60 did not significantly differ between matched solid tumor and malignant ascites.ConclusionsOur results indicate that further expression changes in genes related to glycolysis or oxidative phosphorylation are not a prerequisite for serous cancer cell survival after detachment.

scholarly journals Excessive production of ascitic fluid after laparoscopic operation for early-stage ovarian cancer

2010 ◽  
Vol 8 (1) ◽  
pp. 85-87
Author(s):  
Ioannis Kotsopoulos ◽  
Dimitrios Evaggelinos ◽  
Paraskevi Skafida ◽  
Vasilios Kartsiounis ◽  
Nektarios Chalvatzas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ascitic Fluid ◽  
Early Stage ◽  
Laparoscopic Operation ◽  
Early Stage Ovarian Cancer

scholarly journals Dissimilar tumor cell populations in ascitic fluid of ovarian cancer patients

2020 ◽  
Vol 19 (1) ◽  
pp. 50-58
Author(s):  
E. V. Kaigorodova ◽  
N. V. Fedulova ◽  
M. O. Ochirov ◽  
D. A. Dyakov ◽  
S. V. Molchanov ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Ascitic Fluid ◽  
Cell Populations

The relationship between tumor size and stage in early versus advanced ovarian cancer: A retrospective chart review

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5580-5580
Author(s):  
L. E. Horvath ◽  
T. Werner ◽  
K. Jones
Keyword(s):  
Ovarian Cancer ◽  
Chart Review ◽  
Advanced Disease ◽  
Early Stage ◽  
Abdominal Cavity ◽  
Advanced Ovarian Cancer ◽  
Retrospective Chart Review ◽  
Advanced Stage ◽  
Early Stage Disease ◽  
Stage Disease

5580 Background: Ovarian cancer has a different prognosis between early (I and II) and advanced stage (III and IV). The mechanism of disease progression is unknown, but patients with advanced disease may have a higher propensity for seeding of the abdominal cavity early in the disease process than those with early stage. Theoretically if this is so, then patients with advanced stage should have smaller sized tumors than patients with early stage. Methods: This was a retrospective chart review of patients in the tumor registry in 2003 to 2006. Patients had epithelial ovarian cancer, other cell types were excluded. Only cases with documentation of surgical and pathologic staging and measured dimensions on pathologic specimen were included. Patient stage and all available dimensions measured on diseased ovaries were recorded. The dimensions for each patient were averaged into a single dimension for that patient, and then these measurements were totaled and averaged. Results: There were 110 patients analyzed: 85 with advanced disease, 25 with early stage. The average measurement was 4.8 cm in advanced disease, and was 10.7 cm in early stage disease. This difference was statistically significant (p < 0.001). Conclusions: Overall, patients with early stage ovarian cancer have diseased ovaries that are more than twice as large as those found in advanced disease. This finding supports the fact that early versus advanced ovarian cancer are 2 separate disease processes. Early stage grows locally and does not disseminate, and advanced stage disseminates while the tumor is still relatively small. Theoretically there may be a factor that separates these 2 into different diseases, where advanced disease patients have a substance produced by their tumor that allows for early dissemination, and early stage lacks this substance and only grows locally. Basic science research comparing the tissue microarrays of early versus advanced stage disease may be able to identify this difference. If the difference is found, perhaps therapy can be targeted against this difference. No significant financial relationships to disclose.

scholarly journals Screening for ovarian cancer: Evidences

2017 ◽  
Vol 1 (1) ◽  
pp. 1-7
Author(s):  
Binuma Shrestha ◽  
Bijaya Chandra Acharya
Keyword(s):  
Ovarian Cancer ◽  
Early Stage ◽  
Abdominal Cavity ◽  
Average Risk ◽  
Preventive Healthcare ◽  
Ovarian Cancer Screening ◽  
Early Stage Disease ◽  
Risk Result ◽  
Stage Disease ◽  
Increased Risk

Cancer of the ovary is a leading cause of death among women. Early stage disease are not evident for the incumbent nature of disease in the abdominal cavity. When ovarian cancer is detected and treated while it is still confined to the ovary (stage I), the 5-year survival rate is approximately 90%, but 33% when the disease is diagnosed at stage III or IV. So screening had role in down staging the disease and improve survival. Evidence still does not support screening in average risk women but annual gynecologic examination with pelvic examination is recommended for preventive healthcare. Screening in women with increased risk and inherited risk result in a decrease in the number of deaths in women. For women with mutations in BRCA2, ovarian cancer screening should be initiated between ages 35 and 40.

scholarly journals Usefulness of Monitoring Circulating Tumor Cells as a Therapeutic Biomarker in Melanoma with BRAF Mutation

2020 ◽  
Author(s):  
Ryuhei Okuyama ◽  
Yukiko Kiniwa ◽  
Kenta Nakamura ◽  
Asuka Mikoshiba ◽  
Atsuko Ashida ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Drug Response ◽  
Early Stage ◽  
Stage Iv ◽  
Mek Inhibitor ◽  
Disease Stage ◽  
Mek Inhibitors ◽  
Non Invasive

Abstract Background: Circulating tumor cells (CTCs) are non-invasive biomarkers that could be used to characterize changes in tumors. In this study, we monitored the number of CTCs, as well as the BRAF genotype of individual CTCs. Methods: CTCs were isolated from peripheral blood using a high-density dielectrophoretic microwell array, followed by labeling with melanoma-specific markers (MART-1 and/or gp100) and a leukocyte marker (CD45). Results: Examination of patients with stage 0–III melanoma detected CTCs even in patients with early disease (stage 0 or I). Next, we analyzed CTCs in five patients with stage IV melanoma during treatment with BRAF/MEK inhibitors. The number of CTCs fluctuated in association with the drug response in four of the five patients, suggesting that the total number of CTCs usually reflected the drug response. Interestingly, one of those patients had CTCs with seven different BRAF genotypes, and the mutated CTCs disappeared upon treatment with BRAF/MEK inhibitors, except for those harboring BRAFA598V.Conclusions: CTCs are present even in the early stage of melanoma, and the number of CTCs seems to reflect drug response during treatment with BRAF/MEK inhibitors. Furthermore, genetic heterogeneity of BRAF may contribute to drug resistance of BRAF/MEK inhibitor. Our findings demonstrate the usefulness of CTC analysis in melanoma for monitoring targeted therapies and understanding mechanism of drug resistance.

scholarly journals Epithelial-mesenchymal interconversions in ovarian cancer: the levels and functions of E-cadherin in intraabdominal dissemination

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Ricardo J. Roque ◽  
Margarida Figueiredo Dias ◽  
Filipa Costa Sousa
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cells ◽  
Abdominal Cavity ◽  
Growth Factor Receptor ◽  
Expression Variability ◽  
Epithelial Growth Factor ◽  
Multicellular Aggregates ◽  
Dynamic Expression ◽  
Response To Chemotherapy ◽  
E Cadherin

The metastatic process of ovarian cancer (OC) is almost exclusively defined by direct shedding of tumor cells into the abdominal cavity, followed by clustering into multicellular aggregates and posterior peritoneal anchorage. This process relies on dynamic intercellular interactions which are modified by epithelial-mesenchymal interconversions and, therefore, E-cadherin expression variability. Although widely accepted as a tumor suppressor in many types of cancer, E-cadherin is currently known to have a dynamic expression and a much more complex role in OC. First, high E-cadherin expression is considered a sign of metaplasia in the normal ovarian epithelium, due to its association with epithelial growth factor receptor (EGFR) mediated cell proliferation. Subsequently, it is the decreased expression of E-cadherin that allows the acquisition of a more invasive phenotype, leading to the spread of primary tumor cells into the peritoneal fluid. This downregulation seems to depend on complex regulatory mechanisms, from molecular proteolysis to microenvironment interference and epigenetic regulation. E-cadherin cleavage and its resulting fragments appear to be essential to the process of dissemination and even to the formation of multicellular aggregates. Paradoxically, the maintenance of some E-cadherin expression seems to promote intercellular adhesion, resistance, and survival while decreasing cancer response to chemotherapy. Multiple studies have shown that reversing epithelial-mesenchymal transaction (EMT) and increasing E-cadherin expression prevents OC intraperitoneal dissemination, but findings that simultaneously correlate E-cadherin downregulation to higher chemotherapy sensitivity should not be ignored. Nevertheless, EMT and E-cadherin seem to have a potential interest as therapeutic targets in novel approaches to OC treatment.

scholarly journals Accuracy of Pretreatment Ultrasonography Assessment of Intra-Abdominal Spread in Epithelial Ovarian Cancer: A Prospective Study

Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1600
Author(s):  
Agnieszka Tomasińska ◽  
Maciej Stukan ◽  
Michał Badocha ◽  
Aleksandra Myszewska
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Residual Disease ◽  
Abdominal Cavity ◽  
Preoperative Assessment ◽  
Disease Stage ◽  
Abdominal Ultrasonography ◽  
Predictive Values ◽  
Primary Debulking Surgery ◽  
Surgical Complexity

The aim of this study was to test the accuracy of ultrasonography performed by gynecological oncologists for the preoperative assessment of epithelial ovarian cancer (EOC) spread in the pelvis and abdominal cavity. A prospective, observational cohort study was performed at a single tertiary cancer care unit. Patients with suspected EOC were recruited and underwent comprehensive transvaginal and abdominal ultrasonography performed by a gynecological oncologist. Sixteen intra-abdominal localizations and parameters were assessed using ultrasonography and compared with surgical-pathological status (reference standard). Sensitivity, specificity, positive and negative predictive values, and overall accuracy were calculated. Differences were analyzed using Fisher’s exact and chi-square tests. Ultimately, we included 132 patients (median age 62 years), of whom 67% were in stage IIIC–IVB and 72% had serous cancer. Overall prediction accuracies for the involvement of the omentum, small bowel mesentery root, and frozen pelvis, and detecting ascites were >90%. Detecting the involvement of the pelvis peritoneum, liver and spleen hilum, and rectosigmoid colon, and predictions of disease stage and residual disease had overall accuracies of 80–90%. The lowest accuracy was for involvement of the abdominal peritoneum (69%) and diaphragm peritoneum (right 71%; left 75%) and surgical complexity prediction (77%). Stratification of results by presence or absence of ascites revealed significantly higher specificity of ultrasonography (clinically meaningful) for assessments of the abdominal/pelvic peritoneum, spleen hilum, and rectum wall, if there were ascites. A gynecological oncologist, experienced in surgery and sonology, performing comprehensive ultrasonography on patients with EOC can accurately detect intraperitoneal lesions and recognize critical disease manifestations and predict stage, surgical complexity, and residual disease, which allow accurate qualification of patients for primary debulking surgery or neoadjuvant chemotherapy.

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