LEPTIN PROMOTES A MORE AGGRESIVE BEHAVIOR OF OVARIAN CANCER CELLS: A POTENTIAL EXPLANATION FOR A WORSE PROGNOSIS IN OBESE OVARIAN CANCER PATIENTS: IGCS-0095 Ovarian Cancer

2015 ◽  
Vol 25 (Supp 1) ◽  
pp. 67-67
Author(s):  
M. Cuello-Fredes ◽  
S. Kato ◽  
L. Abarzúa-Catalán ◽  
A. Delpiano ◽  
C. Trigo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Ovarian Cancer Cells ◽  
Potential Explanation ◽  
Worse Prognosis

scholarly journals CircPLEKHM3 acts as a tumor suppressor through regulation of the miR-9/BRCA1/DNAJB6/KLF4/AKT1 axis in ovarian cancer

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Lei Zhang ◽  
Qing Zhou ◽  
Qiongzi Qiu ◽  
Ling Hou ◽  
Mengting Wu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Biology ◽  
Ovarian Cancer Cells ◽  
Ovarian Carcinomas ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Endogenous Expression

Abstract Background Emerging evidence has shown that circular RNAs (circRNAs) play essential roles in cancer biology and are potential biomarkers and targets for cancer therapy. However, the expression and function of circRNAs in ovarian carcinogenesis and its progression remain elusive. Methods RNA sequencing was performed to reveal circRNA expression profiles in ovarian cancerous and normal tissues. Single-molecule RNA in-situ hybridization was used to quantify circPLEKHM3 expression in tumor tissues. Cell-based in-vitro and in-vivo assays were subsequently conducted to support the clinical findings. Results CircPLEKHM3 was identified as one of the most significantly down-regulated circRNAs in ovarian cancer tissues compared with normal tissues. Its expression was further decreased in peritoneal metastatic ovarian carcinomas compared to primary ovarian carcinomas. Patients with lower circPLEKHM3 tend to have a worse prognosis. Functionally, circPLEKHM3 overexpression inhibited cell growth, migration and epithelial–mesenchymal transition, whereas its knockdown exerted an opposite role. Further analyses showed that circPLEKHM3 sponged miR-9 to regulate the endogenous expression of BRCA1, DNAJB6 and KLF4, and consequently inactivate AKT1 signaling. In addition, AKT inhibitor MK-2206 could block the tumor-promoting effect of circPLEKHM3 depletion, and potentiate Taxol-induced growth inhibition of ovarian cancer cells. Conclusions Our findings demonstrated that circPLEKHM3 functions as a tumor suppressor in ovarian cancer cells by targeting the miR-9/BRCA1/DNAJB6/KLF4/AKT1 axis and may be used as a prognostic indicator and therapeutic target in ovarian cancer patients. The new strategy for treating ovarian cancer by a combination therapy of Taxol with MK-2206 is worth further investigation, especially in ovarian cancer patients with loss of circPLEKHM3 expression.

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.

scholarly journals Secretome Identifies Tenascin-X as a Potent Marker of Ovarian Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Marianne Kramer ◽  
Sandra Pierredon ◽  
Pascale Ribaux ◽  
Jean-Christophe Tille ◽  
Patrick Petignat ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Ca 125 ◽  
Ovarian Cancer Cells ◽  
Serous Ovarian Cancer ◽  
Protein Biomarkers ◽  
Serum Samples ◽  
Cancer Tissues

CA-125 has been a valuable marker for the follow-up of ovarian cancer patients but it is not sensitive enough to be used as diagnostic marker. We had already used secretomic methods to identify proteins differentially secreted by serous ovarian cancer cells compared to healthy ovarian cells. Here, we evaluated the secretion of these proteins by ovarian cancer cells during the follow-up of one patient. Proteins that correlated with CA-125 levels were screened using serum samples from ovarian cancer patients as well as benign and healthy controls. Tenascin-X secretion was shown to correlate with CA-125 value in the initial case study. The immunohistochemical detection of increased amount of tenascin-X in ovarian cancer tissues compared to healthy tissues confirms the potent interest in tenascin-X as marker. We then quantified the tenascin-X level in serum of patients and identified tenascin-X as potent marker for ovarian cancer, showing that secretomic analysis is suitable for the identification of protein biomarkers when combined with protein immunoassay. Using this method, we determined tenascin-X as a new potent marker for serous ovarian cancer.

scholarly journals Targeting CA-125 Transcription by Development of a Conditionally Replicative Adenovirus for Ovarian Cancer Treatment

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4265
Author(s):  
Er Yue ◽  
Guangchao Yang ◽  
Yuanfei Yao ◽  
Guangyu Wang ◽  
Atish Mohanty ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Essential Gene ◽  
In Vivo Studies ◽  
Ca 125 ◽  
Ovarian Cancer Cells ◽  
Specific Expression ◽  
Dna Fragment

CA-125, encoded by the MUC16 gene, is highly expressed in most ovarian cancer cells and thus serves as a tumor marker for monitoring disease progression or treatment response in ovarian cancer patients. However, targeting MUC16/CA-125 for ovarian cancer treatment has not been successful to date. In the current study, we performed multiple steps of high-fidelity PCR and obtained a 5 kb DNA fragment upstream of the human MUC16 gene. Reporter assays indicate that this DNA fragment possesses transactivation activity in CA-125-high cancer cells, but not in CA-125-low cancer cells, indicating that the DNA fragment contains the transactivation region that controls specific expression of the MUC16 gene in ovarian cancer cells. We further refined the promoter and found a 1040 bp fragment with similar transcriptional activity and specificity. We used this refined MUC16 promoter to replace the E1A promoter in the adenovirus type 5 genome DNA, where E1A is an essential gene for adenovirus replication. We then generated a conditionally replicative oncolytic adenovirus (CRAd) that replicates in and lyses CA-125-high cancer cells, but not CA-125-low or -negative cancer cells. In vivo studies showed that intraperitoneal virus injection prolonged the survival of NSG mice inoculated intraperitoneally (ip) with selected ovarian cancer cell lines. Furthermore, the CRAd replicates in and lyses primary ovarian cancer cells, but not normal cells, collected from ovarian cancer patients. Collectively, these data indicate that targeting MUC16 transactivation utilizing CRAd is a feasible approach for ovarian cancer treatment that warrants further investigation.

scholarly journals CHI3L1 results in poor outcome of ovarian cancer by promoting properties of stem-like cells

2019 ◽  
Vol 26 (1) ◽  
pp. 73-88 ◽  
Author(s):  
Han-Wei Lin ◽  
Ying-Cheng Chiang ◽  
Nai-Yun Sun ◽  
Yu-Li Chen ◽  
Chi-Fang Chang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Cancer Patients ◽  
Side Population ◽  
Ovarian Cancer Cells ◽  
Tumor Spheroid ◽  
Spheroid Formation ◽  
Poor Outcome

The role of chitinase-3-like protein 1 (CHI3L1) in ovarian cancer and the possible mechanisms were elucidated. CHI3L1 is a secreted glycoprotein and associated with inflammation, fibrosis, asthma, extracellular tissue remodeling and solid tumors. Our previous study showed CHI3L1 could be a potential prognostic biomarker for epithelial ovarian cancer and could protect cancer cells from apoptosis. Therefore, clinical data and quantitation of CHI3L1 of ovarian cancer patients, tumor spheroid formation, side-population assays, Aldefluor and apoptotic assays, ELISA, RT-PCR, immunoblotting and animal experiments were performed in two ovarian cancer cells lines, OVCAR3 and CA5171, and their CHI3L1-overexpressing and -knockdown transfectants. High expression of CHI3L1 was associated with poor outcome and chemoresistance in ovarian cancer patients. The mRNA expression of CHI3L1 in CA5171 ovarian cancer stem-like cells was 3-fold higher than in CA5171 parental cells. CHI3L1 promoted the properties of ovarian cancer stem-like cells including generating more and larger tumor spheroids and a higher percentage of ALDH+ in tumor cells and promoting resistance to cytotoxic drug-induced apoptosis. CHI3L1 could induce both the Akt (essential) and Erk signaling pathways, and then enhance expression of β-catenin followed by SOX2, and finally promote tumor spheroid formation and other properties of ovarian cancer stem-like cells. OVCAR3 CHI3L1-overexpressing transfectants were more tumorigenic in vivo, whereas CA5171 CHI3L1-knockdown transfectants were not tumorigenic in vivo. CHI3L1 critically enhances the properties of ovarian cancer stem-like cells. CHI3L1 or CHI3L1-regulated signaling pathways and molecules could be potential therapeutic targets in ovarian cancer.

scholarly journals The Platelet-Activating Factor Receptor’s Association with the Outcome of Ovarian Cancer Patients and Its Experimental Inhibition by Rupatadine

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2337
Author(s):  
Eileen Deuster ◽  
Ivi Hysenaj ◽  
Maja Kahaly ◽  
Elisa Schmoeckel ◽  
Doris Mayr ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Platelet Activating Factor ◽  
Ovarian Cancer Cells ◽  
Cancer Subtypes ◽  
Therapeutic Implications ◽  
Gene And Protein Expression

The platelet-activating factor receptor (PAFR) and its ligand (PAF) are important inflammatory mediators that are overexpressed in ovarian cancer. The receptor is an important player in ovarian cancer development. In this study, we aimed to evaluate the prognostic value of PAFR in epithelial ovarian cancer (EOC) and the potential use of its antagonist, rupatadine, as an experimental treatment. Tissue microarrays of ovarian cancer patients, most markedly those with a non-mucinous subtype, immunohistochemically overexpressed PAFR. Elevated cytoplasmic PAFR expression was found to significantly and independently impair patients’ overall and recurrence-free survival (OS: median 83.48 vs. 155.03 months; p = 0.022; RFS: median 164.46 vs. 78.03 months; p = 0.015). In vitro, the serous ovarian cancer subtypes especially displayed an elevated PAFR gene and protein expression. siRNA knockdown of PAFR decreased cell proliferation significantly, thus confirming the receptor’s protumorigenic effect on ovarian cancer cells. The clinically approved PAFR antagonist rupatadine effectively inhibited in vitro cell proliferation and migration of ovarian cancer cells. PAFR is a prognostic marker in ovarian cancer patients and its inhibition through rupatadine may have important therapeutic implications in the therapy of ovarian cancer patients.

Interleukin-10 inhibits ovarian cancer cells growth via down regulation of inflammatory cytokine production

2016 ◽  
Vol 4 (1) ◽  
pp. 71-92
Author(s):  
Xi Wang ◽  
Shuhe Yang
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Gynecologic Cancer ◽  
Tumor Development ◽  
Case Fatality ◽  
Interleukin 10 ◽  
Treg Cells ◽  
Western World ◽  
Ovarian Cancer Cells

Ovarian cancer is the most lethal type of gynecologic cancer in the Western world. The high case fatality rate is due in part because most ovarian cancer patients present with advanced stage disease which is essentially incurable. Unfortunately, only a quarter of ovarian cancer patients are diagnosed as stage I. For this reason, considerable efforts have been devoted to the search of novel ovarian cancer markers. Interleukin-10 (IL-10) is a broadly acting immune inhibitory cytokine that is generally thought to support tumor growth. Here, we investigated the regulation of IL-10 expression in normal and cancer ovarian surface epithelial cells. A total of 1 × 293 ovarian cancer cells were inoculated subcutaneously into the left flank of IL-10−/−, IL-10+/+ C57BL/6 background mice. Ovarian cancer cells had accelerated growth in IL-10−/− mice as compared with IL-10+/+ mice as shown by tumor volume measurement. Further, the percentages of intratumoral Treg cells during the course of tumor development were higher in IL-10−/− mice as compared with their wild-type counterparts beginning on day 12. In addition, presenting data showed that myeloid cells from tumor-free mice expressed higher levels of IL-1α and IL-1β in IL-10−/− than IL-10+/+ mice. While the roles of IL-10 in ovarian malignant transformation remain unclear, we propose that IL-10 may represent alternative targets for diagnosis and therapy and of this deadly disease.

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