Endpoint in ovarian cancer xenograft model predicted by nighttime motion metrics

MicroPET is a noninvasive imaging modality that can potentially track tumor development in nude rats using the radiotracer fluorine 18-fluorodeoxyglucose (18F-FDG). Our goal was to determine whether microPET, as opposed to more invasive techniques, could be used to noninvasively monitor the development of ovarian cancer in the peritoneal cavity of nude rats for monitoring treatment response in future studies. Female nude rats were inoculated intraperitoneally with 36 million NIH:OVCAR-3 cells. Imaging was carried out at 2, 4, 6, or 8 weeks postinoculation. Each rat was fasted overnight and intravenously injected with 11.1 MBq (300 μCi) of 18F-FDG in 0.2 mL of saline. Thirty minutes following injection, the rats were placed in the microPET and scanned for 30 min. After imaging, rats were euthanized for ascites and tissue collection for biodistribution and histopathologic correlation. Standard uptake values (SUVs) of 18F-FDG within the peritoneal cavity were also calculated from regions of interest analysis of the microPET images. MicroPET images showed diffuse increased uptake of 18F-FDG throughout the peritoneal cavity of tumor rats (mean SUV = 4.64) compared with control rats (mean SUV = 1.03). Ascites gathered from tumor-bearing rats had increased 18F-FDG uptake as opposed to the peritoneal fluid collected from control rats. Biodistribution data revealed that the percent injected dose per gram (% ID/g) was significantly higher in tumor-bearing rats (6.29%) than in control rats (0.59%) in the peritoneal lymph nodes. Pathology verified that these lymph nodes were more reactive in tumor-bearing rats. By 6 weeks, some rats developed solid masses within the peritoneum, which could be detected on microPET images and confirmed as tumor by histopathology. 18F-FDG uptake in these tumors at necropsy was 2.83% ID/g. These results correlate with previous invasive laparoscopic studies of the same tumor model and demonstrate that microPET using 18F-FDG is a promising noninvasive tool to localize and follow tumor growth in an intraperitoneal ovarian cancer model.

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Detection of Ovarian Cancer Using Samples Sourced from the Vaginal Microenvironment

10.1101/597740 ◽

2019 ◽

Author(s):

Melissa M. Galey ◽

Alexandria N. Young ◽

Valentina Z. Petukhova ◽

Mingxun Wang ◽

Jian Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Disease Progression ◽

Xenograft Model ◽

Screening Methods ◽

Maldi Tof Ms ◽

Analytical Technique ◽

Maldi Tof ◽

Specificity And Sensitivity ◽

Biological Mixtures ◽

Tof Ms

AbstractMass spectrometry (MS) offers high levels of specificity and sensitivity in clinical applications, and we have previously been able to demonstrate that matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS is capable of distinguishing two-component biological mixtures at low limits of detection. Ovarian cancer is notoriously difficult to detect due to the lack of any screening methods for early detection. By sampling a local microenvironment, such as the vaginal fluids, a MS based method is presented that was capable of monitoring disease progression from vaginally collected, local samples from tumor bearing mice. A murine xenograft model of high grade serous ovarian carcinoma (HGSOC) was used for this study and vaginal lavages were obtained from mice on a weekly basis throughout disease progression and subjected to our MALDI-TOF MS workflow followed by statistical analyses. Proteins in the 4-20 kDa region of the mass spectrum could consistently be measured to yield a fingerprint that correlated with disease progression over time. These fingerprints were found to be statistically stable across all mice with the protein fingerprint converging towards the end point of the study. MALDI-TOF MS serves as a unique analytical technique for measuring a sampled vaginal microenvironment in a specific and sensitive manner for the detection of HGSOC in a murine model.

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Identification of a Novel Oncogenic Fusion Gene SPON1-TRIM29 in Clinical Ovarian Cancer That Promotes Cell and Tumor Growth and Enhances Chemoresistance in A2780 Cells

International Journal of Molecular Sciences ◽

10.3390/ijms23020689 ◽

2022 ◽

Vol 23 (2) ◽

pp. 689

Author(s):

Saya Nagasawa ◽

Kazuhiro Ikeda ◽

Daisuke Shintani ◽

Chiujung Yang ◽

Satoru Takeda ◽

...

Keyword(s):

Ovarian Cancer ◽

Rna Sequencing ◽

Anticancer Drugs ◽

Fusion Gene ◽

Xenograft Model ◽

Fusion Transcript ◽

Serous Carcinoma ◽

Fusion Genes ◽

Sequencing Data ◽

Chromosome 11

Gene structure alterations, such as chromosomal rearrangements that develop fusion genes, often contribute to tumorigenesis. It has been shown that the fusion genes identified in public RNA-sequencing datasets are mainly derived from intrachromosomal rearrangements. In this study, we explored fusion transcripts in clinical ovarian cancer specimens based on our RNA-sequencing data. We successfully identified an in-frame fusion transcript SPON1-TRIM29 in chromosome 11 from a recurrent tumor specimen of high-grade serous carcinoma (HGSC), which was not detected in the corresponding primary carcinoma, and validated the expression of the identical fusion transcript in another tumor from a distinct HGSC patient. Ovarian cancer A2780 cells stably expressing SPON1-TRIM29 exhibited an increase in cell growth, whereas a decrease in apoptosis was observed, even in the presence of anticancer drugs. The siRNA-mediated silencing of SPON1-TRIM29 fusion transcript substantially impaired the enhanced growth of A2780 cells expressing the chimeric gene treated with anticancer drugs. Moreover, a subcutaneous xenograft model using athymic mice indicated that SPON1-TRIM29-expressing A2780 cells rapidly generated tumors in vivo compared to control cells, whose growth was significantly repressed by the fusion-specific siRNA administration. Overall, the SPON1-TRIM29 fusion gene could be involved in carcinogenesis and chemotherapy resistance in ovarian cancer, and offers potential use as a diagnostic and therapeutic target for the disease with the fusion transcript.

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GRP137 promotes cell proliferation and metastasis through regulation of the PI3K/AKT pathway in human ovarian cancer

Tumori Journal ◽

10.5301/tj.5000703 ◽

2018 ◽

Vol 104 (5) ◽

pp. 330-337 ◽

Cited By ~ 4

Author(s):

Li-qian Zhang ◽

Su-qing Yang ◽

Xiang-dong Qu ◽

Xian-jun Chen ◽

Hong-sheng Lu ◽

...

Keyword(s):

Ovarian Cancer ◽

G Protein ◽

Biological Activities ◽

Xenograft Model ◽

Akt Pathway ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

G Protein Coupled Receptor ◽

Skov3 Cells ◽

G Protein Coupled

Purpose: Ovarian cancer is one of the leading causes of death for women worldwide. The present study aims to investigate the role of G protein-coupled receptor 137 (GPR137) in the biological activities of ovarian cancer cells. Methods: (QUERY: Please supply Methods for Abstract) Results: G protein-coupled receptor 137 was highly expressed in clinical ovarian cancer tissues and exhibited the highest protein levels in SKOV3 cells and OVCAR3 cells. Knockdown of GPR137 caused significant decreases in cell proliferative rates and colony formation abilities in SKOV3 cells and OVCAR3 cells and also inhibited the in vivo tumorigenesis in a xenograft model. It was observed that knockdown of GPR137 inhibited cell motility by up to 40% in SKOV3 cells and approximately 65% in OVCAR3 cells in wound-healing assay. Cell migration abilities were consistently inhibited by 68.2% in SKOV3 cells and 59.3% in OVCAR3 cells, whereas cell invasion abilities were inhibited by 64.0% and 74.2% in SKOV3 and OVCAR3 cells, respectively, after knockdown of GPR137. When GPR137 was depleted, epithelial markers were increased, while mesenchymal markers decreased. Conclusions: Our data suggest that GPR137 plays pro-oncogenic roles in ovarian cancer via regulation of the PI3K/AKT pathway. These observations might pave new insights into therapeutic strategies against human ovarian cancer.

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Fucosterol Suppresses the Progression of Human Ovarian Cancer by Inducing Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

Marine Drugs ◽

10.3390/md18050261 ◽

2020 ◽

Vol 18 (5) ◽

pp. 261 ◽

Cited By ~ 1

Author(s):

Hyocheol Bae ◽

Jin-Young Lee ◽

Gwonhwa Song ◽

Whasun Lim

Keyword(s):

Ovarian Cancer ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Cancer Cells ◽

Cell Cycle Progression ◽

Xenograft Model ◽

Tumor Formation ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Anticancer Properties

Ovarian cancer is difficult to diagnose early and has high rates of relapse and mortality. Therefore, the treatment of ovarian cancer needs to be improved. Recently, several studies have been conducted in an attempt to develop anticancer drugs from naturally derived ingredients. Compared to traditional chemotherapy, natural compounds can overcome drug resistance with lower side effects. Fucosterol, a phytosterol present in brown algae, reportedly possesses many bioactive effects, including anticancer properties. However, the anticancer effects of fucosterol in ovarian cancer remain unexplored. Therefore, we investigated the effects of fucosterol on progression in human ovarian cancer cells. Fucosterol inhibited cell proliferation and cell-cycle progression in ovarian cancer cells. Additionally, fucosterol regulated the proliferation-related signaling pathways, the production of reactive oxygen species, mitochondrial function, endoplasmic reticulum stress, angiogenesis, and calcium homeostasis. Moreover, it decreased tumor formation in a zebrafish xenograft model. These results indicate that fucosterol could be used as a potential therapeutic agent in ovarian cancer.

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