scholarly journals Progression-Mediated Changes in Mitochondrial Morphology Promotes Adaptation to Hypoxic Peritoneal Conditions in Serous Ovarian Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Joseph P. Grieco ◽  
Mitchell E. Allen ◽  
Justin B. Perry ◽  
Yao Wang ◽  
Yipei Song ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Model ◽  
Gynecological Cancer ◽  
Metastatic Potential ◽  
Adaptation To Hypoxia ◽  
Mitochondrial Morphology ◽  
Serous Ovarian Cancer ◽  
Tumor Initiating Cells ◽  
Mitochondrial Dynamic ◽  
Functional Changes

Ovarian cancer is the deadliest gynecological cancer in women, with a survival rate of less than 30% when the cancer has spread throughout the peritoneal cavity. Aggregation of cancer cells increases their viability and metastatic potential; however, there are limited studies that correlate these functional changes to specific phenotypic alterations. In this study, we investigated changes in mitochondrial morphology and dynamics during malignant transition using our MOSE cell model for progressive serous ovarian cancer. Mitochondrial morphology was changed with increasing malignancy from a filamentous network to single, enlarged organelles due to an imbalance of mitochondrial dynamic proteins (fusion: MFN1/OPA1, fission: DRP1/FIS1). These phenotypic alterations aided the adaptation to hypoxia through the promotion of autophagy and were accompanied by changes in the mitochondrial ultrastructure, mitochondrial membrane potential, and the regulation of reactive oxygen species (ROS) levels. The tumor-initiating cells increased mitochondrial fragmentation after aggregation and exposure to hypoxia that correlated well with our previously observed reduced growth and respiration in spheroids, suggesting that these alterations promote viability in non-permissive conditions. Our identification of such mitochondrial phenotypic changes in malignancy provides a model in which to identify targets for interventions aimed at suppressing metastases.

scholarly journals High-Throughput Sequencing Identification of Differentially Expressed microRNAs in Metastatic Ovarian Cancer with experimental validations

2020 ◽  
Author(s):  
Yang Gu ◽  
Shulan Zhang
Keyword(s):  
Ovarian Cancer ◽  
High Throughput Sequencing ◽  
Human Cancer ◽  
Quantitative Polymerase Chain Reaction ◽  
Gynecological Cancer ◽  
Metastatic Potential ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Downstream Target ◽  
Differentially Expressed Mirnas

Abstract Background: Ovarian cancer (OC) is a common gynecological cancer and characterized by high metastatic potential. MicroRNAs (miRNAs, miRs) have the promise to be harnessed as prognostic and therapeutic biomarkers for OC. Herein, we sought to identify differentially expressed miRNAs and mRNAs in metastatic OC, and to validate them with functional experiments. Methods: Differentially expressed miRNAs and miRNAs were screened from six pairs of primary OC tissues and metastatic tissues using an miRStar™ Human Cancer Focus miRNA & Target mRNA PCR Array. Then, gene expression profiling results were verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The binding affinity between miR-7-5p and TGFβ2 was validated by dual-luciferase reporter assay. Expression of miR-7-5p and TGFβ2 was manipulated to assess their roles in malignant phenotypes of highly metastatic HO-8910PM cells. Results: MiRNA profiling and sequencing identified 12 miRNAs and 10 mRNAs that were differentially expressed in metastatic tissues. Gene ontology and Pathway analyses determined that 3 differentially expressed mRNAs (ITGB3, TGFβ2 and TNC) were related to OC metastasis. The results of RT-qPCR confirmed that the decrease of miR-7-5p was most significant in OC metastasis, while TGFβ2 was up-regulated in OC metastasis. Moreover, miR-7-5p targeted and negatively regulated TGFβ2. MiR-7-5p overexpression accelerated HO-8910PM cell viability and invasion, and TGFβ2 overexpression reversed the results. Meanwhile, simultaneous miR-7-5p and TGFβ2 overexpression rescued the cell activities. Conclusions: This study characterizes differentially expressed miRNAs and mRNAs in metastatic OC, where miR-7-5p and its downstream target were most closely associated with metastatic OC. Overexpression of miR-7-5p targets and inhibits TGFβ2 expression, thereby inhibiting the growth and metastasis of OC.

Abstract SY35-02: Phenotypic heterogeneity and instability of human serous ovarian cancer tumor-initiating cells

2012 ◽  
Author(s):  
Benjamin G. Neel ◽  
Jocelyn M. Stewart ◽  
Bernd Bodenmiller ◽  
Laurie Ailles ◽  
Craig Gedye ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phenotypic Heterogeneity ◽  
Serous Ovarian Cancer ◽  
Tumor Initiating Cells ◽  
Cancer Tumor

scholarly journals Engineered EV-Mimetic Nanoparticles as Therapeutic Delivery Vehicles for High-Grade Serous Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3075
Author(s):  
Amal A. Al-Dossary ◽  
Essam A. Tawfik ◽  
Adaugo C. Isichei ◽  
Xin Sun ◽  
Jiahe Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gynecological Cancer ◽  
Treatment Options ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Delivery Vehicle ◽  
Platinum Drug ◽  
Gynecological Malignancy ◽  
Cancer Chemotherapeutics ◽  
Drug Resistant Strains

High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy among women. Several obstacles impede the early diagnosis and effective treatment options for ovarian cancer (OC) patients, which most importantly include the development of platinum-drug-resistant strains. Currently, extensive efforts are being put into the development of strategies capable of effectively circumventing the physical and biological barriers present in the peritoneal cavity of metastatic OC patients, representing a late stage of gastrointestinal and gynecological cancer with an extremely poor prognosis. Naturally occurring extracellular vesicles (EVs) have been shown to play a pivotal role in progression of OC and are now being harnessed as a delivery vehicle for cancer chemotherapeutics. However, there are limitations to their clinical application due to current challenges in their preparation techniques. Intriguingly, there is a recent drive towards the use of engineered synthetic EVs for the delivery of chemotherapeutics and RNA interference therapy (RNAi), as they show the promise of overcoming the obstacles in the treatment of OC patients. This review discusses the therapeutic application of EVs in OC and elucidates the potential use of engineered EV-mimetic nanoparticles as a delivery vehicle for RNAi therapy and other chemotherapeutics, which would potentially improve clinical outcomes of OC patients.

An organotypic model of high-grade serous ovarian cancer to test the anti-metastatic potential of ROR2 targeted Polyion complex nanoparticles.

2021 ◽  
Author(s):  
Nidhi Joshi ◽  
Dongli Liu ◽  
Deborah Marsh ◽  
Kristie-Ann Dickson ◽  
Caroline Ford ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Peritoneal Cavity ◽  
Metastatic Potential ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Polyion Complex ◽  
Gynaecological Malignancy ◽  
Late Stages

High-grade serous ovarian cancer (HGSOC) is the most lethal gynaecological malignancy. Most patients are diagnosed at late stages when the tumour has metastasised throughout the peritoneal cavity. The Wnt receptor...

scholarly journals High-Throughput Sequencing Identification of Differentially Expressed microRNAs in Metastatic Ovarian Cancer with Experimental Validations

2020 ◽  
Author(s):  
Yang Gu ◽  
Shulan Zhang
Keyword(s):  
Ovarian Cancer ◽  
High Throughput Sequencing ◽  
Human Cancer ◽  
Quantitative Polymerase Chain Reaction ◽  
Gynecological Cancer ◽  
Metastatic Potential ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Downstream Target ◽  
Differentially Expressed Mirnas

Abstract Background: Ovarian cancer (OC) is a common gynecological cancer and characterized by high metastatic potential. MicroRNAs (miRNAs, miRs) have the promise to be harnessed as prognostic and therapeutic biomarkers for OC. Herein, we sought to identify differentially expressed miRNAs and mRNAs in metastatic OC, and to validate them with functional experiments.Methods: Differentially expressed miRNAs and miRNAs were screened from six pairs of primary OC tissues and metastatic tissues using an miRStar™ Human Cancer Focus miRNA & Target mRNA PCR Array. Then, gene expression profiling results were verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The binding affinity between miR-7-5p and TGFβ2 was validated by dual-luciferase reporter assay. Expression of miR-7-5p and TGFβ2 was manipulated to assess their roles in malignant phenotypes of highly metastatic HO-8910PM cells.Results: MiRNA profiling and sequencing identified 12 miRNAs and 10 mRNAs that were differentially expressed in metastatic tissues. Gene ontology and Pathway analyses determined that 3 differentially expressed mRNAs (ITGB3, TGFβ2 and TNC) were related to OC metastasis. The results of RT-qPCR confirmed that the decrease of miR-7-5p was most significant in OC metastasis, while TGFβ2 was up-regulated in OC metastasis. Moreover, miR-7-5p targeted and negatively regulated TGFβ2. MiR-7-5p overexpression accelerated HO-8910PM cell viability and invasion, and TGFβ2 overexpression reversed the results. Meanwhile, simultaneous miR-7-5p and TGFβ2 overexpression rescued the cell activities.Conclusions: This study characterizes differentially expressed miRNAs and mRNAs in metastatic OC, where miR-7-5p and its downstream target were most closely associated with metastatic OC. Overexpression of miR-7-5p targets and inhibits TGFβ2 expression, thereby inhibiting the growth and metastasis of OC.

scholarly journals Quantitative assesment of coexpression of cytokeratins and mesenchimal cells marker vimentin in serous ovarian cancer

2017 ◽  
Vol 16 (4) ◽  
pp. 29-33 ◽  
Author(s):  
T. A. Bogush ◽  
A. A. Arefieva ◽  
S. A. Kaliuzhny ◽  
E. A. Bogush ◽  
S. A. Tjulandin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Cells ◽  
Tumor Cells ◽  
Clinical Significance ◽  
Quantitative Assessment ◽  
Staining Method ◽  
Metastatic Potential ◽  
Expression Level ◽  
Serous Ovarian Cancer ◽  
Double Immunofluorescence

Background. Epithelial-mesenchymal transition (EMT) is a factor related to metastatic potential of tumor cells. The most distinguishing feature of this transformation is expression of protein vimentin, which is not common for epithelial cells. Data of EMT level and clinical significance of the marker is ambiguous in prognosis of tumor different localization including ovarian cancer. Objective is characterization of EMT in ovarian cancer tissue based on quantitative analysis of co-expression level of epithelial cytokeratins and mesenchymal cells marker vimentin. Materials and methods. A quantitative assessment of co-expression level of cytokeratins and vimentin was performed by double immunofluorescence staining method (58 surgery specimens of ovarian cancer stage III), associated with flow cytometry. Results. Double immunofluorescence staining method, developed and used in the current study, was used for quantitative assessment of EMT level based on value of cytokeratin and vimentin co-expression in epithelial cells. Epithelial cells co-expressed these markers, were detected in 100 % tumor investigated with individual value differences from 10 to 86 %. Average co-expression level of cytokeratins and vimentin in subgroups with high and low level value related to median 42 % significantly varied and were 28,5 ± 7,5 and 56,3 ± 11,8 % (p = 0,02) respectively. Conclusions Serous ovarian cancer is molecular heterogeneous group with principal differences in level of EMT tumor phenotype between various patients. In half of the cases the disease is characterized by high metastatic potential of tumor cells. Co-expression of cyto-keratins and vimentin in all the tumors investigated is evidenced clinical significance of this molecular characteristic in ovarian cancer pathogenesis.

scholarly journals Characterization of Candidate Factors Associated With the Metastasis and Progression of High Grade Serous Ovarian Cancer

2021 ◽  
Author(s):  
Huiping Liu ◽  
Ling Zhou ◽  
Hongyan Cheng ◽  
Shang Wang ◽  
Wenqing Luan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Primary Tumor ◽  
Gynecological Cancer ◽  
Wnt Signaling Pathway ◽  
The Cancer Genome Atlas ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Hub Genes ◽  
Bioinformatics Analyses ◽  
Factors Associated

Abstract Background. High grade serous ovarian cancer (HGSOC) is the highest cause of gynecological cancer-related mortality due to the extremely metastatic nature of this disease. The goal of this study is to explore and evaluate the profiles and characteristics of candidate factors associated with metastasis and progression of HGSOC.Methods. Transcriptomic data of HGSOC patients’ samples collected from the primary tumor and matched omental metastatic tumor were obtained from three independent studies in the NCBI GEO database. Genes significantly up-regulated and down-regulated were selected to evaluate the effects to prognosis and progression of ovarian cancer using data of ovarian cancer patients from The Cancer Genome Atlas (TCGA) database. Enrichment analysis for biological processes and pathways was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis. Furthermore, the hub genes immune landscapes were estimated by Tumor Immune Estimation Resource (TIMER) database.Results. 14 candidate genes included ADIPOQ, ALPK2, BARX1, CD37, CNR2, COL5A3, FABP4, FAP, GPR68, ITGBL1, MOXD1, PODNL1, SFRP2 and TRAF3IP3 were selected as up-regulated genes in metastatic tumors in every database while CADPS, GATA4, STAR and TSPAN8 were down-regulated. These 14 genes were significantly enriched for negative regulation of Wnt signaling pathway, fat cell differentiation, extracellular matrix organization. Finally, ALPK2, FAP, SFRP2 and GATA4, STAR, TSPAN8 were selected as hub genes that were found to be significantly associated with the survival and recurrence. All hub genes were correlated with several types of tumor microenvironmental cells infiltration significantly, especially for cancer associated fibroblasts and NK cells.Conclusions. This study indicates that screening for differentially expressed genes and pathways in HGSOC primary tumor and matched metastasis tumor using integrated bioinformatics analyses. In sum, we identify six hub genes correlated with the progression of HGSOC in our study, which might provide effective targets to predict prognosis and provide novel insights into immune-based therapy strategies of HGSOC well.

scholarly journals High-throughput sequencing identification of differentially expressed microRNAs in metastatic ovarian cancer with experimental validations

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yang Gu ◽  
Shulan Zhang
Keyword(s):  
Ovarian Cancer ◽  
High Throughput Sequencing ◽  
Human Cancer ◽  
Quantitative Polymerase Chain Reaction ◽  
Gynecological Cancer ◽  
Metastatic Potential ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Downstream Target ◽  
Differentially Expressed Mirnas

Abstract Background Ovarian cancer (OC) is a common gynecological cancer and characterized by high metastatic potential. MicroRNAs (miRNAs, miRs) have the promise to be harnessed as prognostic and therapeutic biomarkers for OC. Herein, we sought to identify differentially expressed miRNAs and mRNAs in metastatic OC, and to validate them with functional experiments. Methods Differentially expressed miRNAs and mRNAs were screened from six pairs of primary OC tissues and metastatic tissues using a miRStar™ Human Cancer Focus miRNA and Target mRNA PCR Array. Then, gene expression profiling results were verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The binding affinity between miR-7-5p and TGFβ2 was validated by dual-luciferase reporter assay. Expression of miR-7-5p and TGFβ2 was manipulated to assess their roles in malignant phenotypes of highly metastatic HO-8910PM cells. Results MiRNA profiling and sequencing identified 12 miRNAs and 10 mRNAs that were differentially expressed in metastatic tissues. Gene ontology and Pathway analyses determined that 3 differentially expressed mRNAs (ITGB3, TGFβ2 and TNC) were related to OC metastasis. The results of RT-qPCR confirmed that the decrease of miR-7-5p was most significant in OC metastasis, while TGFβ2 was up-regulated in OC metastasis. Moreover, miR-7-5p targeted and negatively regulated TGFβ2. MiR-7-5p overexpression accelerated HO-8910PM cell viability and invasion, and TGFβ2 overexpression reversed the results. Meanwhile, simultaneous miR-7-5p and TGFβ2 overexpression rescued the cell activities. Conclusions This study characterizes differentially expressed miRNAs and mRNAs in metastatic OC, where miR-7-5p and its downstream target were most closely associated with metastatic OC. Overexpression of miR-7-5p targets and inhibits TGFβ2 expression, thereby inhibiting the growth and metastasis of OC.

scholarly journals A brief discussion on the diagnosis and management of Paraneoplastic Neurological Syndromes associated with ovarian cáncer. The importance of not thinking only about what we see

2020 ◽  
pp. 01-06
Keyword(s):  
Ovarian Cancer ◽  
Early Diagnosis ◽  
Myasthenia Gravis ◽  
Primary Tumor ◽  
Early Identification ◽  
Gynecological Cancer ◽  
Paraneoplastic Neurological Syndrome ◽  
Serous Ovarian Cancer ◽  
Neurological Syndrome ◽  
Paraneoplastic Neurological Syndromes

In relation to a recently published case [13] of a patient diagnosed with serous ovarian cancer which began as a paraneoplastic neurological syndrome, myasthenia gravis, here the importance of an early diagnosis of this type and its multidisciplinary handling is discussed. We want to highlight the early identification of the primary tumor and its treatment, in order to avoid the progression of these disorders which can develop into severe, incapacitating, or even fatal, neurological impairments. Keywords: Paraneoplastic Neurological Syndromes; Myasthenia gravis; Ovarian Cancer; Gynecological cancer

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