scholarly journals The role of resveratrol, Sirtuin1 and RXRα as prognostic markers in ovarian cancer

2021 ◽  
Author(s):  
Fangfang Chen ◽  
Thomas Kolben ◽  
Sarah Meister ◽  
Bastian Czogalla ◽  
Theresa M. Kolben ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Prognostic Markers ◽  
Gynecologic Cancer ◽  
Resistance Mechanisms ◽  
Retinoid X Receptor ◽  
Tissue Samples ◽  
Improve Treatment ◽  
Ovarian Cell Lines

Abstract Objective Ovarian cancer is the most lethal gynecologic cancer. Resveratrol (RSV) is known to alter metabolism in cancer. It affects the nuclear retinoid-X-receptor (RXR), which implies a modulating effect of RXR to gynaecologic cancers. Furthermore, RSV targets Sirtuin1 (Sirt1), a histone deacetylase. Study design 123 tissue samples of patients with serous or mucinous ovarian cancer were examined for expression of Sirt1 and RXR. Ovarian cell lines were treated with RSV and consequences on viability and apoptosis were evaluated. The influence of RSV to Sirt1 and RXR expression was analyzed by western blotting Results A correlation of nuclear Sirt1 and RXRα expression could be detected (p = 0.006). Co-expression of nuclear RXRα and cytoplasmic (p = 0.026) or nuclear (p = 0.041) Sirt1 was associated with significantly increased overall survival in advanced tumour stages. Viability was decreased in all cell lines after stimulation with resveratrol, while cell apoptosis was increased. RSV treatment led to significant lower Sirt1 expression in A2780 cells (p = 0.025) and significant increased RXR expression in cisA2780 cells (p = 0.012) Conclusion In order to use RSV as medical target, studies could be developed to improve the understanding of drug resistance mechanisms and consequently improve treatment outcome.

scholarly journals The role of Resveratrol, Sirtuin1 and RXRα as prognostic markers in ovarian cancer

2021 ◽  
Author(s):  
Fangfang Chen ◽  
Thomas Kolben ◽  
Sarah Meister ◽  
Bastian Czogalla ◽  
Theresa M Kolben ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Prognostic Markers ◽  
Gynecologic Cancer ◽  
Resistance Mechanisms ◽  
Tissue Samples ◽  
Advanced Tumor ◽  
Ovarian Cell Lines ◽  
Tumor Stages

Abstract Objective: Ovarian cancer is the most lethal gynecologic cancer. Resveratrol (RSV) is known to alter metabolism in cancer. It affects the nuclear retinoid-X-receptor (RXR), which implies a modulating effect of RXR to gynecologic cancers. Furthermore, RSV targets Sirtuin1 (Sirt1), a histone deacetylase. Study design: 123 tissue samples of patients with serous or mucinous ovarian cancer were examined for expression of Sirt1 and RXR. Ovarian cell-lines were treated with RSV and consequences on viability and apoptosis were evaluated. The influence of RSV to Sirt1 and RXR expression was analyzed by western blotting. Results: A correlation of nuclear Sirt1 and RXRα expression could be detected (p=0.006). Co-expression of nuclear RXRα and cytoplasmic (p=0.026) or nuclear (p=0.041) Sirt1 was associated with significantly increased overall survival in advanced tumor stages. Viability was decreased in all cell-lines after stimulation with resveratrol, while cell apoptosis was increased. RSV treatment led to significant lower Sirt1 expression in A2780 cells (p=0.025) and significant increased RXR expression in cisA2780 cells (p=0.012). Conclusion: In order to use RSV as medical target, studies could be developed to improve the understanding of drug resistance mechanisms and consequently improve treatment outcome.

scholarly journals New insights into the role of PTCH1 protein in serous ovarian carcinomas

2021 ◽  
Author(s):  
Valentina Karin-Kujundzic ◽  
Adriana Covarrubias-Pinto ◽  
Anita Skrtic ◽  
Semir Vranic ◽  
Ljiljana Serman
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Cell Lines ◽  
Expression Level ◽  
Tumor Promoter ◽  
Protein Expression Level ◽  
Ovarian Carcinomas ◽  
Tissue Samples ◽  
Serous Ovarian Carcinoma

Abstract Background The Hedgehog (Hh) signaling pathway is essential for normal embryonic development, while its hyperactivation in adult organism is associated with development of various cancers, including ovarian cancer. The role of the Hh signaling pathway in ovarian cancer, as well as in certain histological subtypes of ovarian cancer, is poorly understood. Therefore, we investigated the role of PTCH1 protein and changes in the promoter methylation status of the corresponding gene, in a cohort of low- (LGSC) and high-grade (HGSC) serous ovarian carcinomas and HGSC cell lines (OVCAR5, OVCAR8 and OVSAHO). Methods PTCH1 protein expression level was analyzed using immunohistochemistry in tissue samples, and by immunofluorescence and Western blot in cell lines. DNA methylation pattern of PTCH1 gene were analyzed by methylation-specific PCR (MSP). Mann-Whitney U test was used to compare differences in expression of PTCH1 protein among ovarian tumor samples compared with normal tissue samples, while Spearman’s correlation was used to test the association between DNA promoter methylation of the PTCH1 gene and expression of the corresponding protein. Results PTCH1 protein expression level was significantly higher in HGSCs and LGSCs compared with control tissues (healthy ovaries and fallopian tubes). Similarly, cancer cell lines exhibited significantly higher PTCH1 protein expression in comparison with normal fallopian tube non-ciliated epithelium cell line (FNE1). Nuclear localization of the PTCH1 protein in tumor tissue and cultured tumor cells suggests that this protein could play an active tumor promoter role in the nuclei of serous ovarian carcinoma cells. PTCH1 protein fragments of different molecular weights were detected in the cell lines, indicating possible proteolytic cleavage of this protein, resulting in the generation of soluble N-terminal fragments that are translocated to the nucleus. DNA methylation of the PTCH1 gene promoter was not in line with the expression level of this protein, suggesting that possibly other mechanisms, either epigenetic or posttranslational, regulate PTCH1 gene expression and protein level in serous ovarian carcinomas. Conclusions Our results indicate that PTCH1 protein could play an active tumor promoter role in the pathogenesis of serous ovarian carcinoma.

scholarly journals G Protein-Coupled Receptors (GPCRs)-Mediated Calcium Signaling in Ovarian Cancer: Focus on GPCRs activated by Neurotransmitters and Inflammation-Associated Molecules

2019 ◽  
Vol 20 (22) ◽  
pp. 5568 ◽  
Author(s):  
Predescu ◽  
Crețoiu ◽  
Crețoiu ◽  
Pavelescu ◽  
Suciu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Chemokine Receptors ◽  
Ovarian Cell Lines ◽  
Different Types ◽  
Protein Receptors ◽  
Essential Contribution ◽  
Molecular Signals ◽  
G Protein Coupled

G-coupled protein receptors (GCPR) involve several signaling pathways, some of them being coupled with intracellular calcium (Ca2+) mobilization. GPCRs were involved in migration, invasion and metastasis of different types of cancers, including ovarian cancer. Many studies have discussed the essential contribution of GPCRs activated by steroid hormones in ovarian cancer. However, ovarian cancer is also associated with altered signals coming from the nervous system, the immune system or the inflammatory environment, in which GPCRs are ‘sensing’ these molecular signals. Many studies have been oriented so far on ovarian cell lines (most of them being of human cell lines), and only few studies based on animal models or clinical studies have been devoted to the expression changes or functional role of GPCRs in ovarian cancer. In this paper, we review the alterations of GPCRs activated by neurotransmitters (muscarinic receptors, serotonin receptors, dopamine receptors, adrenoceptors) or inflammation-associated molecules (bradykinin receptors, histamine receptors, chemokine receptors) in ovarian cancer and we discuss their potential as histological biomarkers.

scholarly journals Long non-coding RNA NEAT1 facilitates the growth, migration, and invasion of ovarian cancer cells via the let-7 g/MEST/ATGL axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lili Yin ◽  
Yu Wang
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Loss Of Function ◽  
Tissue Samples ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background/Aim Growing evidence indicates a significant role of long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) in ovarian cancer, a frequently occurring malignant tumor in women; however, the possible effects of an interplay of NEAT1 with microRNA (miRNA or miR) let-7 g in ovarian cancer are not known. The current study aimed to investigate the role of the NEAT1/let-7 g axis in the growth, migration, and invasion of ovarian cancer cells and explore underlying mechanisms. Methods NEAT1 expression levels were examined in clinical tissue samples and cell lines. The relationships between NEAT1, let-7 g, and MEST were then analyzed. Gain- or loss-of-function approaches were used to manipulate NEAT1 and let-7 g. The effects of NEAT1 on cell proliferation, migration, invasion, and apoptosis were evaluated. Mouse xenograft models of ovarian cancer cells were established to verify the function of NEAT1 in vivo. Results NEAT1 expression was elevated while let-7 g was decreased in ovarian cancer clinical tissue samples and cell lines. A negative correlation existed between NEAT1 and let-7 g, whereby NEAT1 competitively bound to let-7 g and consequently down-regulate let-7 g expression. By this mechanism, the growth, migration, and invasion of ovarian cancer cells were stimulated. In addition, let-7 g targeted mesoderm specific transcript (MEST) and inhibited its expression, leading to promotion of adipose triglyceride lipase (ATGL) expression and inhibition of ovarian cancer cell growth, migration, and invasion. However, the effect of let-7 g was abolished by overexpression of MEST. Furthermore, silencing of NEAT1 decreased the xenograft tumor growth by decreasing MEST while up-regulating let-7 g and ATGL. Conclusions Cumulatively, the findings demonstrated that NEAT1 could promote malignant phenotypes of ovarian cancer cells by regulating the let-7 g/MEST/ATGL signaling axis. Therefore, NEAT1 can be regarded as an important molecular target and biomarker for ovarian cancer.

scholarly journals Role of notch pathway and HNF1 in cell death induced by HDACs inhibitors in ovarian cancer cell lines, serous and clear cells

2010 ◽  
Vol 4 (S2) ◽  
Author(s):  
Fernanda Silva ◽  
Jacinta Serpa ◽  
Germana Domingues ◽  
Gabriela Silva ◽  
António Almeida ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Notch Pathway ◽  
Cancer Cell Lines ◽  
Clear Cells ◽  
Ovarian Cancer Cell Lines

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.

The role of the glucocorticoid receptor (GR) in inhibiting chemotherapy-induced apoptosis in high-grade serous ovarian carcinoma (HGS-OvCa).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11101-11101
Author(s):  
Erica Michelle Stringer ◽  
Maxwell N. Skor ◽  
Gini F. Fleming ◽  
Suzanne D. Conzen
Keyword(s):  
Ovarian Cancer ◽  
Glucocorticoid Receptor ◽  
Tumor Cell ◽  
Cell Survival ◽  
Cell Lines ◽  
High Grade ◽  
Induced Apoptosis ◽  
Er Alpha ◽  
Ovca Cell

11101 Background: Ovarian cancer is the leading cause of death from gynecologic malignancies. High-grade serous ovarian cancer (HGS-OvCa) is often initially sensitive to platinum-based therapy, but relapse rates remain high. The TCGA recently found that HGS-OvCas have a gene expression and mutational profile similar to that of triple negative breast cancer (TNBC). Previously, our group demonstrated that dexamethasone treatment decreased chemotherapy-induced tumor cell apoptosis in TNBC and HGS-OvCa cell lines. We have also shown that glucocorticoid receptor (GR) activation induces expression of anti-apoptotic genes SGK1 and MKP1/DUSP1 in both HGS-OvCa and TNBC cell lines and in primary human ovarian and TNBC tumors. Methods: We examined glucocorticoid receptor (GR), estrogen receptor (ER), and progesterone receptor (PR) expression in a panel of HGS-OvCa cell lines by Western analysis and qRT-PCR. We also performed apoptosis assays with and without mifepristone, glucocorticoid and/or chemotherapy treatment using IncuCyte live-cell imaging technology in order to measure the effect of GR modulation of chemotherapy sensitivity. Results: HGS-OvCa cell lines (including CAOV3, HeyA8, SKOV3, Monty-1) all had detectable GR expression; HeyA8, SKOV3, and Monty-1 cell lines expressed very low levels of ER-alpha while all other HGS-OvCa cell lines did not express any detectable ER-alpha. Furthermore, none of the HGS-OvCa cell lines tested expressed PR.Apoptosis assays revealed that GR activation significantly inhibited gemcitabine/carboplatin-induced apoptosis in HGS-OvCa cell lines and that mifepristone could reverse this cell survival effect, presumably through GR antagonism. Conclusions: These results suggest that treatment with mifepristone, a GR antagonist, reverses GR-mediated cell survival signaling in HGS-OvCa and increases chemotherapy-induced tumor cell death. To further investigate the role of GR activity in HGS-OvCa, we are currently performing xenograft experiments with chemotherapy +/- mifepristone treatment.

Clinical Trials in Recurrent Ovarian Cancer

2011 ◽  
Vol 21 (4) ◽  
pp. 771-775 ◽  
Author(s):  
Michael Friedlander ◽  
Edward Trimble ◽  
Anna Tinker ◽  
David Alberts ◽  
Elisabeth Avall-Lundqvist ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Gynecologic Cancer ◽  
Recurrent Ovarian Cancer ◽  
Consensus Conference ◽  
Ca 125 ◽  
Therapeutic Approaches ◽  
Cooperative Research ◽  
International Consensus

The 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup was held in Vancouver, Canada, in June 2010. Representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. Group C, 1 of the 3 discussion groups, examined recurrent ovarian cancer, and we report the consensus reached regarding 4 questions. These included the following: (1) What is the role of cytoreductive surgery for recurrent ovarian cancer? (2) How do we define distinct patient populations in need of specific therapeutic approaches? (3) Should end points for trials with recurrent disease vary from those of first-line trials? (4) Is CA-125 progression alone sufficient for entry/eligibility into clinical trials?

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