Molecular, cellular and systemic aspects of epithelial ovarian cancer and its tumor microenvironment

Schoutrop, Esther; Moyano‐Galceran, Lidia; Lheureux, Stéphanie; Mattsson, Jonas; Lehti, Kaisa; Dahlstrand, Hanna; Magalhaes, Isabelle

doi:10.1016/j.semcancer.2022.03.027

Cited by 52 publications

(41 citation statements)

References 267 publications

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“…Due to population-based screening tools being ineffective or less effective for OC, it is necessary to develop new approaches for early diagnosis and prevention of OC [ 6 ]. The therapeutic outcomes of most cases are largely limited by acquired chemoradioresistance and poor development of targeted therapies, ultimately experiencing disease recurrence [ 7 , 8 ]. For patients with platinum-resistant OC, the response to further chemotherapy is poor with median survival lower than one year [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

lncRNA DARS-AS1 Modulates TSPAN1-Mediated ITGA2 Hypomethylation by Interaction with miR-194-5p Thus Promoting Ovarian Cancer Progression

Jun

Gao

Chen

et al. 2022

Stem Cells International

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Objective. Ovarian cancer (OC) is usually called the “silent killer” due to its asymptomatic characteristics until advanced stages, thus being a significant threat to female health worldwide. In this work, we characterized an oncogenic DARS-AS1 role in OC. Methods. The aggressiveness behaviors of the OC cell model were examined by CCK-8 assay, transwell invasion assay, flow cytometry, and immunoblotting analysis of apoptosis-related proteins. Interactions of miR-194-5p with lncRNA DARS-AS1 or TSPAN1 and of TSPAN1 with ITGA2 were validated by using a luciferase activity assay and chromatin immunoprecipitation (ChIP) assay. Results. The OC cell model exhibited overexpressed lncRNA DARS-AS1 compared to normal cells. lncRNA DARS-AS1 knockdown led to reduced OC cell growth and metastasis while inducing the apoptosis in the OC cell model. lncRNA DARS-AS1 positively regulated TSPAN1 expression by binding with miR-194-5p and TSPAN1-mediated ITGA2 hypomethylation in OC cells. Further rescue function studies demonstrated that lncRNA DARS-AS1 affected OC cell viability, migration, invasion, and apoptosis ability by modulating miR-194-5p and TSPAN1 expressions. Conclusion. Our work demonstrates that lncRNA DARS-AS1 promotes OC progression by modulating TSPAN1 and ITGA2 hypomethylation by binding with miR-194-5p.

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Section: Introductionmentioning

confidence: 99%

lncRNA DARS-AS1 Modulates TSPAN1-Mediated ITGA2 Hypomethylation by Interaction with miR-194-5p Thus Promoting Ovarian Cancer Progression

Jun

Gao

Chen

et al. 2022

Stem Cells International

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“…Ovarian cancer is reported as one of the most prevalent pathologies in gynecological oncology. This malignancy is characterized as epithelial or non-epithelial [ 11 ], and can be categorized into further subgroups: low-grade and high-grade serous cancer, [ 3 ] endometrioid, clear-cell, and mucinous ovarian cancer [ 12 ]. Many genes have been implicated in pathogenesis, with the most prevalent being the p53, KRAS, PTEN, and MEK and their related signalling pathways.…”

Section: Introductionmentioning

confidence: 99%

“…Many genes have been implicated in pathogenesis, with the most prevalent being the p53, KRAS, PTEN, and MEK and their related signalling pathways. Due to the lack of specific symptoms, and as they exhibit sporadic distribution (only 5–10% of cases are correlated with family history), 70% of ovarian cancer cases are detected in the advanced stages [ 13 ], thus having the lowest survival rate among all gynecological cancers [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Intraoperative Flow Cytometry for the Characterization of Gynecological Malignancies

Anastasiadi

Mantziou

Akrivis

et al. 2022

Biology

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Cell-cycle analysis has shown the presence of aneuploidy to be associated with poor prognosis. We developed an innovative rapid cell-cycle analysis protocol (the Ioannina protocol) that permitted the intraoperative identification of neoplastic cells in a plethora of malignancies. Herein, we aimed to investigate the potential role of cell-cycle analysis in the intraoperative characterization of gynecological malignancies. Women who underwent surgery for gynecological malignancies in our institution over a three-year period were included in this study. Permanent section pathology evaluation was used as the gold standard for malignancy evaluation. Total accordance was observed between flow cytometry and pathology evaluation. In total, 21 aneuploid cancers were detected following DNA index calculation. Of these, 20 were hyperploid and 1 was hypoploid. In addition, tumor samples were characterized by a significantly lower percentage of cells in G0/G1, as well as an induced tumor index. The response time for flow cytometry to obtain results was 5–6 min per sample. It seems that flow cytometry analyses for intraoperative tumor evaluation can be safely expanded to gynecological malignancies. This is a novel practical approach that has been proven valuable in several tumor types to date, and also seems to be reliable for gynecological malignancies. Intraoperative flow cytometry is expected to be crucial in decisions of lymph node dissection in endometrial cancers, due to its rapid response regarding the tumor invasion of part or all of the myometrial thickness. In this way, the surgeon can quickly modify the plane of dissection. Our results warrant the further investigation of applying iFC in larger, multicenter studies.

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“…The standard management approach in the treatment of epithelial ovarian cancer includes cytoreductive surgery and platinumbased chemotherapy. [1][2][3][4][5][6] Cytoreductive surgery aims to remove cancerous tissue from the ovaries and adjacent tissues to achieve optimal debulking. Chemotherapy is usually employed either in the neoadjuvant setting (to downstage cancer) or after cytoreductive surgery (to treat microscopic seedling in optimally debulked tumors or reduce tumor burden in suboptimally debulked cancer).…”

Section: Introductionmentioning

confidence: 99%

“…Chemotherapy is usually employed either in the neoadjuvant setting (to downstage cancer) or after cytoreductive surgery (to treat microscopic seedling in optimally debulked tumors or reduce tumor burden in suboptimally debulked cancer). [1][2][3][4][5][6] Despite advances in these treatment modalities, the overall outcomes for patients with epithelial ovarian cancer remain poor with over 4000 patients dying from the condition each year in the UK. However, recent advances in ovarian cancer therapeutics have had a positive impact in improving survival outcomes.…”

Section: Introductionmentioning

confidence: 99%

Towards Personalized Management of Ovarian Cancer

Algethami¹,

Kulkarni²,

Sadiq³

et al. 2022

CMAR

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Despite advances in surgery and chemotherapy, the overall outcomes for patients with advanced ovarian cancer remain poor. Although initial response rates to platinum-based chemotherapy is about 60–80%, most patients will have recurrence and succumb to the disease. However, a DNA repair–directed precision medicine strategy has recently generated real hope in improving survival. The clinical development of PARP inhibitors has transformed lives for many patients with BRCA germline-deficient and/or platinum-sensitive epithelial ovarian cancers. Antiangiogenic agents and intraperitoneal chemotherapy approaches may also improve outcomes in patients. Moreover, evolving immunotherapeutic opportunities could also positively impact patient outcomes. Here we review the current clinical state of PARP inhibitors and other clinically viable targeted approaches in ovarian cancer.

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Molecular, cellular and systemic aspects of epithelial ovarian cancer and its tumor microenvironment

Cited by 52 publications

References 267 publications

lncRNA DARS-AS1 Modulates TSPAN1-Mediated ITGA2 Hypomethylation by Interaction with miR-194-5p Thus Promoting Ovarian Cancer Progression

lncRNA DARS-AS1 Modulates TSPAN1-Mediated ITGA2 Hypomethylation by Interaction with miR-194-5p Thus Promoting Ovarian Cancer Progression

Intraoperative Flow Cytometry for the Characterization of Gynecological Malignancies

Towards Personalized Management of Ovarian Cancer

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