GENOMIC AND TRANSCRIPTOME PROFILING OF EPITHELIAL OVARIAN CANCER

2008 ◽  
Vol 31 (4) ◽  
pp. 17
Author(s):  
Rebecca JZ Menzies ◽  
Yury V Bukhman ◽  
Nancy F Ng ◽  
Patricia A Shaw ◽  
Tak W Mak
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Early Stage ◽  
Snp Array ◽  
Ovarian Tumors ◽  
Ca 125 ◽  
Molecular Heterogeneity ◽  
Presenting Symptoms

Background: Epithelial ovarian cancer is the leading cause of death by gynecological malignancy. Due to inadequate screening modalities, a lack of characteristic presenting symptoms, limited treatments and a poor understanding of the molecular underpinnings of the disease, only 25% of ovarian cancers are diagnosed at an early stage. Current 5-year survival rates range from 80%, for disease diagnosed in Stage I to as low as 13% for Stage IV. Current screening for ovarian cancer involves measuring CA-125 levels. However, CA-125 testing has low sensitivity since it can be elevated in a variety of other gynecological diseases. Numerous studies have found molecular heterogeneity between the four histological subtypes of ovarian cancer (serous, endometrioid, clear cell and mucinous). However, treatments remain the same for all subtypes regardless of molecular heterogeneity. Thus, better treatment targets and biomarkers must be found for this disease. Methods:In our study 300 ovarian tumors will be genomically profiled using the Affymetrix Genome-Wide SNP Array 6.0 to identify loci and genes implicated in ovarian cancer. To date, 51 ovarian tumors have been analyzed using the SNP array. Results:Preliminary analysis of copy number variation in these tumors using Partek software has revealed a total of 978 loci. Known amplifications derived from the literature were seen at CCNE1 and ERBB2. Similarly, well known deletions ofp53 and RB1 in ovarian cancer were detected. Novel amplified loci at 18q11.2 and 4q33 were also detected. Novel deletions were detected at 7p13 and 8q22.2. Conclusion: Future work will include running the remaining 249 tumor samples on the SNP array and analyzing the complete dataset using Partek software. Future validation of identified genes in vitro and in vivo may provide insight and possible biomarkers that may be used clinically to benefit the ovarian cancer patient.

scholarly journals Snail Driving Alternative Splicing of CD44 by ESRP1 Enhances Invasion and Migration in Epithelial Ovarian Cancer

2017 ◽  
Vol 43 (6) ◽  
pp. 2489-2504 ◽  
Author(s):  
Le Chen ◽  
Ying Yao ◽  
Lijuan Sun ◽  
Jiajia Zhou ◽  
Minmin Miao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Alternative Splicing ◽  
Epithelial Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Regulatory Protein ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background/Aims: Our study aims to investigate the role, effect and mechanisms of ESRP1 (epithelial splicing regulatory protein 1) in epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). Methods: Microarray and immunohistochemical analysis of ESRP1 expression were performed in EOC cases. The correlations between ESRP1 expression and clinical factors on EOC were assessed. Lentivirus-mediated RNA interference and EGFP vector which contains ESRP1 gene were used to down-regulate and up-regulate ESRP1 expression in human EOC cell lines. Roles of ESRP1 in cell growth, migration and invasion of EOC cells were also measured by Cell Counting Kit-8 and Transwell systems in vitro and by a nude mice intraperitoneal transplantation model in vivo. Results: By the analysis of Gene Expression Omnibus (GEO) (p<0.05) and our own microarray data (p<0.001), ESRP1 expression in EOC was significantly different from normal ovarian tissue. It was abundant in the nuclei of cancer cells and in malignant lesions. However, it was weakly expressed or negative in both normal and benign lesions. High ESRP1 expression in EOC was associated with poor clinical outcomes. Decreased ESRP1 expression significantly increased cell migration and invasion both in vivo and in vitro. Snail strongly repressed ESRP1 transcription through binding to the ESRP1 promoter in EOC cells. Furthermore, ESRP1 regulated the expression of CD44s. Down-regulated ESRP1 resulted in an isoform switching from CD44v to CD44s, which modulated epithelial-mesenchymal transition (EMT) program in EOC. Up-regulatin of ESRP1 was detected in mesenchymal to epithelial transition (MET) in vivo. Conclusions: ESRP1 regulates CD44 alternative splicing during the EMT process which plays an important role in EOC carcinogenesis. In addition, ESRP1 is associated with disease prognosis in EOC.

scholarly journals Long non-coding RNA PTPRG-AS1 promotes cell tumorigenicity in epithelial ovarian cancer by decoying microRNA-545-3p and consequently enhancing HDAC4 expression

2020 ◽  
Author(s):  
Juanjuan Shi ◽  
Xijian Xu ◽  
Dan Zhang ◽  
Jiuyan Zhang ◽  
Hui Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Epithelial Ovarian Cancer ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background: Long non-coding RNA PTPRG antisense RNA 1 (PTPRG-AS1) deregulation has been reported in various human malignancies and identified as an important modulator of cancer development. Few reports have focused on the detailed role of PTPRG-AS1 in epithelial ovarian cancer (EOC) and its underlying mechanism. This study aimed to determine the physiological function of PTPRG-AS1 in EOC. A series of experiments were also performed to identify the mechanisms through which PTPRG-AS1 exerts its function in EOC.Methods: Reverse transcription-quantitative polymerase chain reaction was used to determine PTPRG-AS1 expression in EOC tissues and cell lines. PTPRG-AS1 was silenced in EOC cells and studied with respect to cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. The putative miRNAs that target PTPRG-AS1 were predicted using bioinformatics analysis and further confirmed in luciferase reporter and RNA immunoprecipitation assays.Results: Our data verified the upregulation of PTPRG-AS1 in EOC tissues and cell lines. High PTPRG-AS1 expression was associated with shorter overall survival in patients with EOC. Functionally, EOC cell proliferation, migration, invasion in vitro, and tumor growth in vivo were suppressed by PTPRG-AS1 silencing. In contrast, cell apoptosis was promoted by loss of PTPRG-AS1. Regarding the mechanism, PTPRG-AS1 could serve as a competing endogenous RNA in EOC cells by decoying microRNA-545-3p (miR-545-3p), thereby elevating histone deacetylase 4 (HDAC4) expression. Furthermore, rescue experiments revealed that PTPRG-AS1 knockdown-mediated effects on EOC cells were, in part, counteracted by the inhibition of miR-545-3p or restoration of HDAC4.Conclusions: PTPRG-AS1 functioned as an oncogenic lncRNA that aggravated the malignancy of EOC through the miR-545-3p/HDAC4 ceRNA network. Thus, targeting the PTPRG-AS1/miR-545-3p/HDAC4 pathway may be a novel strategy for EOC anticancer therapy.

scholarly journals Increase Paclitaxel Sensitivity to Better Suppress Serous Epithelial Ovarian Cancer via Ablating Androgen Receptor/Aryl Hydrocarbon Receptor-ABCG2 Axis

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 463 ◽  
Author(s):  
Wei-Min Chung ◽  
Yen-Ping Ho ◽  
Wei-Chun Chang ◽  
Yuan-Chang Dai ◽  
Lumin Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Androgen Receptor ◽  
Epithelial Ovarian Cancer ◽  
Aryl Hydrocarbon Receptor ◽  
Proximal Promoter ◽  
Luciferase Reporter ◽  
Aryl Hydrocarbon ◽  
Paclitaxel Treatment

Background: Epithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies and presents chemoresistance after chemotherapy treatment. Androgen receptor (AR) has been known to participate in proliferation. Yet the mechanisms of the resistance of this drug and its linkage to the AR remains unclear. Methods: To elucidate AR-related paclitaxel sensitivity, co-IP, luciferase reporter assay and ChIP assay were performed to identify that AR direct-regulated ABCG2 expression under paclitaxel treatment. IHC staining by AR antibody presented higher AR expression in serous-type patients than other types. AR degradation enhancer (ASC-J9) was used to examine paclitaxel-associated and paclitaxel-resistant cytotoxicity in vitro and in vivo. Results: We found AR/aryl hydrocarbon receptor (AhR)-mediates ABCG2 expression and leads to a change in paclitaxel cytotoxicity/sensitivity in EOC serous subtype cell lines. Molecular mechanism study showed that paclitaxel activated AR transactivity and bound to alternative ARE in the ABCG2 proximal promoter region. To identify AR as a potential therapeutic target, the ASC-J9 was used to re-sensitize paclitaxel-resistant EOC tumors upon paclitaxel treatment in vitro and in vivo. Conclusion: The results demonstrated that activation of AR transactivity beyond the androgen-associated biological effect. This novel AR mechanism explains that degradation of AR is the most effective therapeutic strategy for treating AR-positive EOC serous subtype.

scholarly journals Identification of PLK1 as a New Therapeutic Target in Mucinous Ovarian Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 672 ◽  
Author(s):  
Roberta Affatato ◽  
Laura Carrassa ◽  
Rosaria Chilà ◽  
Monica Lupi ◽  
Valentina Restelli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
High Throughput Screening ◽  
Therapeutic Option ◽  
Xenograft Model ◽  
Antimitotic Drugs ◽  
M Phase ◽  
Sirna Library

Mucinous epithelial ovarian cancer (mEOC) is a rare subset of epithelial ovarian cancer. When diagnosed at a late stage, its prognosis is very poor, as it is quite chemo-resistant. To find new therapeutic options for mEOC, we performed high-throughput screening using a siRNA library directed against human protein kinases in a mEOC cell line, and polo-like kinase1 (PLK1) was identified as the kinase whose downregulation interfered with cell proliferation. Both PLK1 siRNA and two specific PLK1 inhibitors (onvansertib and volasertib) were able to inhibit cell growth, induce apoptosis and block cells in the G2/M phase of the cell cycle. We evaluated, in vitro, the combinations of PLK1 inhibitors and different chemotherapeutic drugs currently used in the treatment of mEOC, and we observed a synergistic effect of PLK1 inhibitors and antimitotic drugs. When translated into an in vivo xenograft model, the combination of onvansertib and paclitaxel resulted in stronger tumor regressions and in a longer mice survival than the single treatments. These effects were associated with a higher induction of mitotic block and induction of apoptosis, similarly to what was observed in vitro. These data suggest that the combination onvansertib/paclitaxel could represent a new active therapeutic option in mEOC.

Total Inhibin Is a Potential Serum Marker for Epithelial Ovarian Cancer

2007 ◽  
Vol 92 (7) ◽  
pp. 2526-2531 ◽  
Author(s):  
Anastasia Tsigkou ◽  
Daniele Marrelli ◽  
Fernando M. Reis ◽  
Stefano Luisi ◽  
Agnaldo L. Silva-Filho ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Postmenopausal Women ◽  
Serum Marker ◽  
Ovarian Tumors ◽  
Ca 125 ◽  
Surgical Removal ◽  
Specific Marker ◽  
Ovarian Cancers ◽  
Blood Specimens

Abstract Context: Total inhibin is the sum of precursors, subunits, and mature molecules of inhibin, which the normal ovary nearly stops to produce after menopause, whereas ovarian tumors still release. Objective: The aim of the present study was to evaluate whether the serum concentration of total inhibin has the sensitivity/specificity characteristics to become a diagnostic test for epithelial ovarian cancer in postmenopausal women. Design: This was a controlled, cross-sectional study. Setting: The study was conducted at the University of Siena. Patients: Blood specimens were collected from postmenopausal women with: 1) epithelial ovarian cancer, stage II-III (n = 89); 2) benign ovarian tumors (n = 25); 3) breast (n = 10), colon (n = 10), and stomach (n = 10) cancers; and 4) controls (n = 95). In the group of women with epithelial ovarian cancer, blood specimens were also collected after surgical removal of the tumor. In four cases of women with stage IIC mucinous tumor, blood specimens were collected during the follow-up time. Intervention: Total inhibin was measured by a new double-antibody ELISA. Results: Women with epithelial ovarian cancers showed serum total inhibin levels significantly higher than those with benign tumor or with nonovarian tumors or controls (P &lt; 0.001). Patients with serous (n = 40) or mucinous tumors (n = 17) showed the highest total inhibin levels (P &lt; 0.001). At 95% specificity, the total inhibin assay detected 37 of 40 (93%) serous tumors and 16 of 17 (94%) mucinous tumors. When total inhibin was combined with CA-125, all cases of serous and mucinous tumors were detected, and the overall sensitivity for epithelial ovarian cancers was 99% at 95% specificity. A significant decrease of total inhibin levels was shown in women with serous and mucinous carcinoma as result of surgery (P &lt; 0.001). In the four women who were followed up, recurrence was associated to an increase of total inhibin levels. Conclusions: The present data show that total inhibin is a sensitive and specific marker of epithelial ovarian cancers in postmenopausal women. Total inhibin may therefore be combined with CA-125 for noninvasive diagnosis of epithelial ovarian cancer and may also be a useful serum marker to monitor disease-free intervals.

Randomized, multicenter, two-dose level, open-label, phase IIa study with the intraperitoneally infused trifunctional bispecific antibody catumaxomab (anti-EpCAM × anti-CD3) to select the better dose level in platinum refractory epithelial ovarian cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5556-5556 ◽  
Author(s):  
A. Belau ◽  
J. Pfisterer ◽  
P. Wimberger ◽  
C. Kurzeder ◽  
A. Du Bois ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Dose Level ◽  
Dose Effect ◽  
High Dose ◽  
Specific Cell ◽  
Open Label ◽  
Platinum Refractory

5556 Background: The trifunctional antibody catumaxomab specifically binds EpCAM+ tumor cells, CD3+ T lymphocytes and accessory cells via the Fcγ RI/III thereby inducing a tumor specific cell mediated cytotoxicity in vitro and in vivo. This study was conducted to evaluate efficacy and safety of two different regimens of catumaxomab. Methods: Women with platinum-refractory (progressing during or ≤ 6 mos. after the last platinum containing regimen) epithelial ovarian cancer and measurable recurrent disease were randomized to receive either 10 -10 -10 - 10 μg or 10–20–50–100 μg of catumaxomab over 6h i.p on days 0, 3, 7 and 10. Results: 45 pts. were entered (22 high dose (HD)-arm, 23 low dose (LD)-arm). Both groups were well balanced concerning ECOG-perfomance score, with a median age of 65.6y in the HD- and 57.6y in the LD-arm and with a median diameter of measurable lesions of 90mm in the HD- and 104mm in the LD-arm. Based on the AEs, changes in laboratory parameters and other safety variables observed in the safety population in the course of this study, the accumulated safety experience is consistent with the key features of the mode of action of catumaxomab. Their intensity on median level was mostly mild to moderate. A clinical benefit was detectable in 27.3% of pts. for the HD- (1PR/5SD) and 8.7% of pts. for the LD-arm (2SD). After a median follow-up of 4.96 months, the median overall survival time was 182 d for the HD- and 114 d for the LD-arm. Conclusion: The results demonstrate that catumaxomab is safe with acceptable toxicity when administered as a sequence of 4 IP infusions at 10, 20, 50 and 100 μg. A modest dose effect is observed for the higher doses of catumaxomab. No significant financial relationships to disclose.

scholarly journals MicroRNA-137 suppresses tumor growth in epithelial ovarian cancer in vitro and in vivo

2015 ◽  
Vol 12 (2) ◽  
pp. 3107-3114 ◽  
Author(s):  
LIYU ZHANG ◽  
ZHIHONG LI ◽  
FENGCHUN GAI ◽  
YANPING WANG
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Epithelial Ovarian Cancer

scholarly journals EPDR1, Which Is Negatively Regulated by miR-429, Suppresses Epithelial Ovarian Cancer Progression via PI3K/AKT Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhendan Zhao ◽  
Zhiling Wang ◽  
Pengling Wang ◽  
Shujie Liu ◽  
Yingwei Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Figo Stage ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gynecology And Obstetrics

Epithelial ovarian cancer (EOC) is the main pathological type of ovarian cancer. In this study, we found that ependymin-related 1 (EPDR1) was remarkably downregulated in EOC tissues, and low EPDR1 expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage, metastasis, and poor prognosis. We confirmed that EPDR1 overexpression dramatically suppressed EOC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, EPDR1 inhibited EOC tumorigenesis and progression, at least in part, through the repression of the PI3K (Phosphoinositide 3-kinase)/AKT (AKT Serine/Threonine Kinase 1) signaling pathway. Furthermore, the expression and function of EPDR1 were regulated by miR-429, as demonstrated by luciferase reporter assays and rescue experiments. In conclusion, our study validated that EPDR1, negatively regulated by miR-429, played an important role as a tumor-suppressor gene in EOC development via inhibition of the PI3K/AKT pathway. The miR-429/EPDR1 axis might provide novel therapeutic targets for individualized treatment of EOC patients in the future.

scholarly journals Long Non-coding RNA PTPRG-AS1 Promotes Cell Tumorigenicity in Epithelial Ovarian Cancer by Decoying microRNA-545-3p and Consequently Enhancing HDAC4 Expression

2020 ◽  
Author(s):  
Juanjuan Shi ◽  
Xijian Xu ◽  
Dan Zhang ◽  
Jiuyan Zhang ◽  
Hui Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Epithelial Ovarian Cancer ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background: Long non-coding RNA PTPRG antisense RNA 1 (PTPRG-AS1) deregulation has been reported in various human malignancies and identified as an important modulator of cancer development. Few reports have focused on the detailed role of PTPRG-AS1 in epithelial ovarian cancer (EOC) and its underlying mechanism. This study aimed to determine the physiological function of PTPRG-AS1 in EOC. A series of experiments were also done to identify the mechanisms through which PTPRG-AS1 exerts its function in EOC.Methods: Reverse transcription-quantitative polymerase chain reaction was used to determine PTPRG-AS1 expression in EOC tissues and cell lines. PTPRG-AS1 was silenced in EOC cells and studied with respect to cell proliferation, apoptosis, migration, invasion in vitro, and tumor growth in vivo. The putative miRNAs that target PTPRG-AS1 were predicted using bioinformatics analysis and further confirmed in luciferase reporter and RNA immunoprecipitation assays.Results: Our data verified the upregulation of PTPRG-AS1 in EOC tissues and cell lines. High PTPRG-AS1 expression was associated with shorter overall survival in patients with EOC. Functionally, EOC cell proliferation, migration, invasion in vitro and tumor growth in vivo were suppressed by PTPRG-AS1 silencing. In contrast, cell apoptosis was promoted by loss of PTPRG-AS1. For the mechanism part, PTPRG-AS1 could serve as a competing endogenous RNA in EOC cells by decoying microRNA-545-3p (miR-545-3p), thereby elevating histone deacetylase 4 (HDAC4) expression. Furthermore, rescue experiments revealed that PTPRG-AS1 knockdown-mediated effects on EOC cells were, in part, counteracted by the inhibition of miR-545-3p or restoration of HDAC4.Conclusions: PTPRG-AS1 functioned as an oncogenic lncRNA that aggravated the malignancy of EOC through the miR-545-3p/HDAC4 ceRNA network. Thus, targeting the PTPRG-AS1/miR-545-3p/HDAC4 pathway may be a novel strategy for EOC anticancer therapy.

scholarly journals Role of PET/CT in Assessment of Recurrent Ovarian Tumors

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
S Kadry ◽  
A Haggag ◽  
A Ekbal
Keyword(s):  
Ovarian Cancer ◽  
Tumor Marker ◽  
Early Stage ◽  
Ovarian Tumors ◽  
University Hospital ◽  
Ca 125 ◽  
Early Stage Disease ◽  
Major Health Problem ◽  
Pet Ct ◽  
Suspected Recurrence

Abstract Background Ovarian cancer remains a major health problem worldwide, with over 225,000 new cases and 140,000 deaths reported annually. Despite high response after initial treatment, 20-30% of patients with early-stage disease and up to 75% of patients with advanced disease present with recurrence within two years. Early diagnosis of recurrence is crucial for determination of the best treatment. Aim of the Work is to detect the significance of PET/CT in the early detection of recurrent ovarian tumors. Patients and Method The study included 25 patients who have been diagnosed with ovarian cancer, received treatment and achieved complete response. All of the 25 patients had suspected recurrence either due to elevated tumor markers or suspicious clinical findings. The 25 patients have been referred for PET/CT scan at ElDemerdash university hospital from July 2017 to August 2018. Results Total of 25 patients were included in the study. 18 of 25 patients had high tumor marker (CA 125) level. The remaining 7 patients had suspected recurrence with normal tumor marker levels. Recurrence was confirmed by histopathology or clinical and imaging follow up in 19 patients of the 25 patients. Recurrent disease was not shown in 5 of 19 patients on CECT imaging and 1 of 19 patients on PET/CT imaging. PET/CT had a sensitivity of (94.74%), specificity of (100%) and accuracy of (96%). CECT has been reported with sensitivity of (73.68), specificity of (83.33%) and accuracy of (76%). Conclusion PET/CT is a useful tool and has a higher sensitivity, specificity and accuracy than CECT in detection of recurrent ovarian cancer.

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