scholarly journals Epigenetic silencing of BLU through interfering apoptosis results in chemoresistance and poor prognosis of ovarian serous carcinoma patients

2013 ◽  
Vol 20 (2) ◽  
pp. 213-227 ◽  
Author(s):  
Ying-Cheng Chiang ◽  
Ming-Cheng Chang ◽  
Pao-Jen Chen ◽  
Meei-Maan Wu ◽  
Chang-Yao Hsieh ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Multivariate Analysis ◽  
Poor Prognosis ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Serous Carcinoma ◽  
Ovarian Cancer Cells ◽  
Advanced Stage ◽  
Ovarian Serous Carcinoma

Epithelial ovarian carcinoma is usually present at the advanced stage, during which the patients generally have poor prognosis. Our study aimed to evaluate the correlation of gene methylation and the clinical outcome of patients with advanced-stage, high-grade ovarian serous carcinoma. The methylation status of eight candidate genes was first evaluated by methylation-specific PCR and capillary electrophoresis to select three potential genes including DAPK, CDH1, and BLU (ZMYND10) from the exercise group of 40 patients. The methylation status of these three genes was further investigated in the validation group consisting of 136 patients. Patients with methylated BLU had significantly shorter progression-free survival (PFS; hazard ratio (HR) 1.48, 95% CI 1.01–2.56, P=0.013) and overall survival (OS; HR 1.83, 95% CI 1.07–3.11, P=0.027) in the multivariate analysis. Methylation of BLU was also an independent risk factor for 58 patients undergoing optimal debulking surgery for PFS (HR 2.37, 95% CI 1.03–5.42, P=0.043) and OS (HR 3.96, 95% CI 1.45–10.81, P=0.007) in the multivariate analysis. A possible mechanism of BLU in chemoresistance was investigated in ovarian cancer cell lines by in vitro apoptotic assays. In vitro studies have shown that BLU could upregulate the expression of BAX and enhance the effect of paclitaxel-induced apoptosis in ovarian cancer cells. Our study suggested that methylation of BLU could be a potential prognostic biomarker for advanced ovarian serous carcinoma.

scholarly journals Knockdown of BRCA2 enhances cisplatin and cisplatin-induced autophagy in ovarian cancer cells

2018 ◽  
Vol 25 (1) ◽  
pp. 69-82 ◽  
Author(s):  
Biao Wan ◽  
Leheyi Dai ◽  
Li Wang ◽  
Ying Zhang ◽  
Hong Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Median Time ◽  
Progression Free Survival ◽  
Ovarian Cancer Cells ◽  
Intact Cells ◽  
Ovarian Cancer Cell Lines ◽  
Tumor Tissues ◽  
Cancer Tissues

Clinical implications of the BRCA2 expression level on treatments of ovarian cancer are controversial. Here, we demonstrated that platinum-resistant cancer had a higher percentage of high BRCA2 level (87.5% vs 43.6%, P = 0.001), and that patients with a low BRCA2 level in cancer tissues had longer progression-free survival (with a median time of 28.0 vs 12.0 months, P < 0.001) and platinum-free duration (with a median time of 19.0 vs 5.0 months, P < 0.001) compared with those with a high BRCA2 level. In human ovarian cancer cell lines CAOV-3 and ES-2, cisplatin induced an upregulation of the RAD51 protein, which was inhibited after silencing BRCA2; silencing BRCA2 enhanced the action of cisplatin in vitro and in vivo. Knockdown of BRCA2 promoted cisplatin-induced autophagy. Interestingly, the autophagy blocker chloroquine enhanced cisplatin in BRCA2-silenced cells accompanied by an increase in apoptotic cells, which did not occur in BRCA2-intact cells; chloroquine enhanced the efficacy of cisplatin against BRCA2-silenced CAOV-3 tumors in vivo, with an increase in LC3-II level in tumor tissues. Sensitization of cisplatin was also observed in BRCA2-silenced CAOV-3 cells after inhibiting ATG7, confirming that chloroquine modulated the sensitivity via the autophagy pathway. These data suggest that a low BRCA2 level can predict better platinum sensitivity and prognosis, and that the modulation of autophagy can be a chemosensitizer for certain cancers.

scholarly journals Reduced Gonadotrophin Receptor Expression Is Associated with a More Aggressive Ovarian Cancer Phenotype

2020 ◽  
Vol 22 (1) ◽  
pp. 71
Author(s):  
Janelle Cheung ◽  
Noor A. Lokman ◽  
Riya D. Abraham ◽  
Anne M. Macpherson ◽  
Eunice Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Progression Free Survival ◽  
Receptor Expression ◽  
Ovarian Cancer Cells ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cancer Phenotype

Follicle-stimulating hormone (FSH) and luteinising hormone (LH) play important roles in regulating cell growth and proliferation in the ovary. However, few studies have explored the expression of FSH and LH receptors (FSHR and LHCGR) in ovarian cancer, and their functional roles in cancer progression remain inconclusive. This study investigated the potential impact of both mRNA (FSHR, LHCGR) and protein (FSHR, LHCGR) expression on ovarian cancer progression using publicly available online databases, qRT-PCR (high grade serous ovarian cancers, HGSOC, n = 29 and benign ovarian tumors, n = 17) and immunohistochemistry (HGSOC, n = 144). In addition, we investigated the effect of FSHR and LHCGR siRNA knockdown on the pro-metastatic behavior of serous ovarian cancer cells in vitro. High FSHR or high LHCGR expression in patients with all subtypes of high-grade ovarian cancer was significantly associated with longer progression-free survival (PFS) and overall survival (OS). High FSHR protein expression was associated with increased PFS (p = 0.050) and OS (p = 0.025). HGSOC patients with both high FSHR and high LHCGR protein levels had the best survival outcome, whilst both low FSHR and low LHCGR expression was associated with poorest survival (p = 0.019). Knockdown of FSHR significantly increased the invasion of serous ovarian cancer cells (OVCAR3 and COV362) in vitro. LHCGR knockdown also promoted invasion of COV362 cells. This study highlights that lower FSHR and LHCGR expression is associated with a more aggressive epithelial ovarian cancer phenotype and promotes pro-metastatic behaviour.

scholarly journals Expression of Fatty Acid Synthase Depends on NAC1 and Is Associated with Recurrent Ovarian Serous Carcinomas

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Stefanie M. Ueda ◽  
Kai Lee Yap ◽  
Ben Davidson ◽  
Yuan Tian ◽  
Vivek Murthy ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthase ◽  
Dominant Negative ◽  
Serous Carcinoma ◽  
Ovarian Cancer Cells ◽  
Primary Tumors ◽  
Ovarian Serous Carcinoma ◽  
Skov3 Cells

Our previous reports demonstrated that NAC1, a BTB/POZ domain-containing nuclear protein, upregulates in recurrent ovarian serous carcinoma and participates in developing drug resistance in cancer cells. The current study applies quantitative proteomics to identify the proteins controlled by NAC1 by comparing the proteomes of SKOV3 cells with and without expression of a dominant negative NAC1 construct, N130. From the proteins that are downregulated by N130 (upregulated by NAC1), we chose to further characterize fatty acid synthase (FASN). Similar to change in protein level, the FASN transcript level in SKOV3 cells was significantly reduced by N130 induction or by NAC1 knockdown. Immunohistochemistry showed that NAC1 and FASN immunointensities in ovarian serous carcinoma tissues had a highly significant correlation (P<.0001). Moreover, we found that recurrent serous carcinomas exhibited higher FASN immunointensities than their matched primary tumors (P<.001). Multivariate analysis showed that an FASN staining score of >1 in serous carcinomas was associated with a worse overall survival time (P<.01). Finally, C93, a new FASN inhibitor, induced massive apoptosis in carboplatin/paclitaxel resistant ovarian cancer cells. In conclusion, we show that NAC1 is essential for FASN expression in ovarian serous carcinomas and the expression of FASN significantly correlates with tumor recurrence and disease aggressiveness. The dependence of drug resistant tumor cells on FASN suggests a potential application of FASN-based therapeutics for recurrent ovarian cancer patients.

scholarly journals Jejunal Fistula Complicating Ovarian Serous Carcinoma: Case Report of a Rare Phenomenon and Review of the Literature

2019 ◽  
pp. 1
Author(s):  
Isin Ureyen ◽  
Tayfun Toptas ◽  
Sezin Ates Tatar ◽  
Gulsum Ekin ◽  
Faruk Gulec ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Abdominal Pain ◽  
Digestive System ◽  
The Other ◽  
Serous Carcinoma ◽  
Fistula Formation ◽  
Ovarian Cancer Cells ◽  
Review Of The Literature ◽  
Ovarian Serous Carcinoma ◽  
Small Intestines

<p>Invasion of the wall of the digestive system by ovarian cancer cells isn’t so rare. On the other hand, fistula formation between the tumor and digestive system is an uncommon status. We described a patient with ovarian serous carcinoma that was fistulized into jejenum and formed a region composed of stool and tumor surrounded and limited by small intestines recognized during surgery. This diagnosis should be kept in mind while preparing a patient for ovarian cancer surgery if the patient has acute abdomen or abdominal pain incompatible with the extent of the tumor.</p>

scholarly journals The potent cytotoxicity effect of thymoquinone on Chinese ovarian carcinoma cell line HO-8910 mediated by activating autophagy pathway.

2021 ◽  
Author(s):  
runzhi zhu ◽  
Fei Ye ◽  
Xitong Wang ◽  
Tian Xia ◽  
Xiao Yuan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Nigella Sativa ◽  
Bioactive Compound ◽  
Chinese Patient ◽  
Chinese Patients ◽  
Serous Carcinoma ◽  
Ovarian Cancer Cells ◽  
Ovarian Carcinoma Cell Line ◽  
Gynecological Malignancy

Abstract Ovarian cancer is known for its highest mortality rate in gynecological malignancy. Previous studies demonstrated that thymoquinone (TQ), a bioactive compound isolated from Nigella sativa L., is a potent anti-ovarian cancer agent, which inhibit tumor growth by modulating apoptotic activity. In this study, we found that the effect of chemotherapy on ovarian cancer cells in vitro varies by race/ethnicity. HO-8910 was established from Chinese patient with ovarian serous carcinoma. The results showed that HO-8910 displayed higher resistance to platinum than SKOV3. And further cell variability assay indicated that TQ exhibited dramatically inhibitory activity on HO-8910 and SKOV3. However, apoptosis and cell cycle analysis suggested TQ had multiple mechanisms for its cytotoxic effect. As for HO-8910, TQ could modulated expression level of several pivotal factors involving autophagy, including PI3K, ATG-7, Bectlin-1 and p62, but has little effect on p53, PARP and caspase-3, and no effect on Bax. Our results sustained that TQ was a promising anti-ovarian cancer candidate and its potential application in Chinese patients, even Asian patients , treatment in clinic.

Cytotoxic effects of disulfiram and synergism with cisplatin on ovarian cancer cells in vitro

2018 ◽  
Author(s):  
F Guo ◽  
Z Yang ◽  
J Xu ◽  
J Sehouli ◽  
AE Albers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cytotoxic Effects

Targeting Membrane Receptors of Ovarian Cancer Cells for Therapy

2019 ◽  
Vol 19 (6) ◽  
pp. 449-467
Author(s):  
Zhiquan Liang ◽  
Ziwen Lu ◽  
Yafei Zhang ◽  
Dongsheng Shang ◽  
Ruyan Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Receptor Binding ◽  
Cytoreductive Surgery ◽  
Therapeutic Strategies ◽  
Membrane Receptors ◽  
Ovarian Cancer Cells ◽  
Advanced Stage ◽  
Targeted Therapeutics ◽  
Cellular Processes

Ovarian cancer is a leading cause of death worldwide from gynecological malignancies, mainly because there are few early symptoms and the disease is generally diagnosed at an advanced stage. In addition, despite the effectiveness of cytoreductive surgery for ovarian cancer and the high response rates to chemotherapy, survival has improved little over the last 20 years. The management of patients with ovarian cancer also remains similar despite studies showing striking differences and heterogeneity among different subtypes. It is therefore clear that novel targeted therapeutics are urgently needed to improve clinical outcomes for ovarian cancer. To that end, several membrane receptors associated with pivotal cellular processes and often aberrantly overexpressed in ovarian cancer cells have emerged as potential targets for receptor-mediated therapeutic strategies including specific agents and multifunctional delivery systems based on ligand-receptor binding. This review focuses on the profiles and potentials of such strategies proposed for ovarian cancer treatment and imaging.

scholarly journals Electrochemotherapy with Calcium Chloride and 17β-Estradiol Modulated Viability and Apoptosis Pathway in Human Ovarian Cancer

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 19
Author(s):  
Zofia Łapińska ◽  
Michał Dębiński ◽  
Anna Szewczyk ◽  
Anna Choromańska ◽  
Julita Kulbacka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Calcium Chloride ◽  
Morphological Changes ◽  
Cell Membrane Permeability ◽  
Immunocytochemical Staining ◽  
Ovarian Cancer Cells ◽  
Apoptosis Pathway ◽  
17Β Estradiol

Estrogens (Es) play a significant role in the carcinogenesis and progression of ovarian malignancies. Depending on the concentration, Es may have a protective or toxic effect on cells. Moreover, they can directly or indirectly affect the activity of membrane ion channels. In the presented study, we investigated in vitro the effectiveness of the ovarian cancer cells (MDAH-2774) pre-incubation with 17β-estradiol (E2; 10 µM) in the conventional chemotherapy (CT) and electrochemotherapy (ECT) with cisplatin or calcium chloride. We used three different protocols of electroporation including microseconds (µsEP) and nanoseconds (nsEP) range. The cytotoxic effect of the applied treatment was examined by the MTT assay. We used fluorescent staining and holotomographic imaging to observe morphological changes. The immunocytochemical staining evaluated the expression of the caspase-12. The electroporation process’s effectiveness was analyzed by a flow cytometer using the Yo-Pro™-1 dye absorption assay. We found that pre-incubation of ovarian cancer cells with 17β-estradiol may effectively enhance the chemo- and electrochemotherapy with cisplatin and calcium chloride. At the same time, estradiol reduced the effectiveness of electroporation, which may indicate that the mechanism of increasing the effectiveness of ECT by E2 is not related to the change of cell membrane permeability.

scholarly journals Genetic Perturbation of Pyruvate Dehydrogenase Kinase 1 Modulates Growth, Angiogenesis and Metabolic Pathways in Ovarian Cancer Xenografts

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 325
Author(s):  
Carolina Venturoli ◽  
Ilaria Piga ◽  
Matteo Curtarello ◽  
Martina Verza ◽  
Giovanni Esposito ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Metabolic Pathways ◽  
Negative Impact ◽  
Digital Pathology ◽  
Pyruvate Dehydrogenase Kinase ◽  
Ovarian Cancer Cells ◽  
Pyruvate Dehydrogenase Kinase 1

Pyruvate dehydrogenase kinase 1 (PDK1) blockade triggers are well characterized in vitro metabolic alterations in cancer cells, including reduced glycolysis and increased glucose oxidation. Here, by gene expression profiling and digital pathology-mediated quantification of in situ markers in tumors, we investigated effects of PDK1 silencing on growth, angiogenesis and metabolic features of tumor xenografts formed by highly glycolytic OC316 and OVCAR3 ovarian cancer cells. Notably, at variance with the moderate antiproliferative effects observed in vitro, we found a dramatic negative impact of PDK1 silencing on tumor growth. These findings were associated with reduced angiogenesis and increased necrosis in the OC316 and OVCAR3 tumor models, respectively. Analysis of viable tumor areas uncovered increased proliferation as well as increased apoptosis in PDK1-silenced OVCAR3 tumors. Moreover, RNA profiling disclosed increased glucose catabolic pathways—comprising both oxidative phosphorylation and glycolysis—in PDK1-silenced OVCAR3 tumors, in line with the high mitotic activity detected in the viable rim of these tumors. Altogether, our findings add new evidence in support of a link between tumor metabolism and angiogenesis and remark on the importance of investigating net effects of modulations of metabolic pathways in the context of the tumor microenvironment.

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