Xenograft and Transgenic Mouse Models of Epithelial Ovarian Cancer and Non‐Invasive Imaging Modalities to Monitor Ovarian Tumor Growth In Situ: Applications in Evaluating Novel Therapeutic Agents

2009 ◽  
Vol 45 (1) ◽  
Author(s):  
Denise C. Connolly ◽  
Harvey H. Hensley
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Epithelial Ovarian Cancer ◽  
Mouse Models ◽  
Ovarian Tumor ◽  
Therapeutic Agents ◽  
Transgenic Mouse Models ◽  
Non Invasive ◽  
Novel Therapeutic

Causes and Consequences of Cancer-Associated Thrombocytosis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. SCI-33-SCI-33
Author(s):  
Anil Sood ◽  
Rebecca L. Stone ◽  
Vahid Afshar-Kharghan
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Epithelial Ovarian Cancer ◽  
Mouse Models ◽  
Interleukin 6 ◽  
Conflicts Of Interest ◽  
Chemotherapeutic Agents ◽  
Antibody Treatment ◽  
Platelet Counts ◽  
Tumor Bearing

Abstract Platelets represent one of the largest storage pools of angiogenic and oncogenic growth factors in the human body. The observation that thrombocytosis (platelet count >450,000/µL) occurs in patients with solid malignancies was made over 100 years ago. However, mechanisms of paraneoplastic thrombocytosis and the role that platelets play in abetting cancer growth are unclear. We have used clinical data coupled with sophisticated mouse models to identify the mechanisms and biological implications of paraneoplastic thrombocytosis. Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti-interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an anti-platelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis. Biologically, platelets were detected within the tumor microenvironment and affected tumor growth and response to chemotherapeutic agents. These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. Blocking the stimulatory effects of platelets may have implications for new therapeutic approaches. Disclosures: No relevant conflicts of interest to declare.

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.

Immune cells of the epithelial ovarian cancer microenvironment

2021 ◽  
pp. 67-78
Author(s):  
Varvara Nikolaevna Zhurman ◽  
Natalia Gennadevna Plekhova ◽  
Ekaterina Valeryevna Eliseeva
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Immune Cells ◽  
Ovarian Tumor ◽  
Biologically Active ◽  
Cancer Microenvironment ◽  
Review Of The Literature ◽  
Prognostic Role ◽  
Active Substances

The article is a review of the literature, which analyzes the data on the role of cells of the immune system, cytokines and other biologically active substances secreted by them in the interstitial space of an ovarian tumor. The emphasis is made on the mechanism of realization by immune cells of the stimulating and suppressing action on the development of the tumor. Considerable attention is paid to the prognostic role of immune cells in the development of epithelial ovarian cancer.

scholarly journals Subsequent Development of Epithelial Ovarian Cancer After Ovarian Surgery for Benign Ovarian Tumor: A Population-Based Cohort Study

2020 ◽  
Vol Volume 12 ◽  
pp. 637-649 ◽  
Author(s):  
Chen-Yu Huang ◽  
Wen-Hsun Chang ◽  
Hsin-Yi Huang ◽  
Chao-Yu Guo ◽  
Yiing-Jenq Chou ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cohort Study ◽  
Epithelial Ovarian Cancer ◽  
Ovarian Tumor ◽  
Subsequent Development ◽  
Population Based ◽  
Benign Ovarian Tumor ◽  
Ovarian Surgery

scholarly journals Integrin-Linked Kinase Is a Novel Therapeutic Target in Ovarian Cancer

2020 ◽  
Vol 10 (4) ◽  
pp. 246
Author(s):  
Michael A. Ulm ◽  
Tiffany M. Redfern ◽  
Ben R. Wilson ◽  
Suriyan Ponnusamy ◽  
Sarah Asemota ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Tumor Growth ◽  
Therapeutic Target ◽  
Molecular Heterogeneity ◽  
Ovarian Cells ◽  
Skov3 Cells ◽  
Integrin Linked Kinase ◽  
Cancerous Cells ◽  
Novel Therapeutic

Objective: The objective of this study is to identify and validate novel therapeutic target(s) in ovarian cancer. Background: Development of targeted therapeutics in ovarian cancer has been limited by molecular heterogeneity. Although gene expression datasets are available, most of them lack appropriate pair-matched controls to define the alterations that result in the transformation of normal ovarian cells to cancerous cells. Methods: We used microarray to compare the gene expression of treatment-naïve ovarian cancer tissue samples to pair-matched normal adjacent ovarian tissue from 24 patients. Ingenuity Pathway Analysis (IPA) was used to identify target pathways for further analysis. Integrin-linked kinase (ILK) expression in SKOV3 and OV90 cells was determined using Western blot. ILK was knocked down using CRISPR/Cas9 constructs. Subcutaneous xenograft study to determine the effect of ILK knockdown on tumor growth was performed in NOD SCID gamma mice. Results: Significant upregulation of the ILK pathway was identified in 22 of the 24 cancer specimens, identifying it as a potential player that could contribute to the transformation of normal ovarian cells to cancerous cells. Knockdown of ILK in SKOV3 cells resulted in decreased cell proliferation and tumor growth, and inhibition of downstream kinase, AKT (protein kinase B). These results were further validated using an ILK-1 chemical inhibitor, compound 22. Conclusion: Our initial findings validate ILK as a potential therapeutic target for molecular inhibition in ovarian cancer, which warrants further investigation.

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