scholarly journals Docosahexaenoic acid alone and in combination with carboplatin significantly reduces tumor cell growth in preclinical models of ovarian cancer

2020 ◽  
Author(s):  
Olena Bilyk ◽  
Bahareh Hamedi ◽  
Indrani Dutta ◽  
Marnie Newell ◽  
Amirali B. Bukhari ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Docosahexaenoic Acid ◽  
Tumor Growth ◽  
Dietary Intervention ◽  
Control Diet ◽  
Human Consumption ◽  
Preclinical Models ◽  
Conventional Chemotherapy ◽  
Gynecological Malignancy ◽  
Anti Cancer

ABSTRACTDespite recent advances in diagnosis and treatment, ovarian cancer (OC) is the most lethal gynecological malignancy and improving the efficacy of chemotherapy is of great interest. This study increases our understanding of how dietary intervention with docosahexaenoic acid (DHA)-a supplement proven safe for human consumption – enhances the anti-cancer effects of conventional chemotherapy. Our results demonstrated synergistic cell killing by DHA and carboplatin in OC cell lines. Furthermore, DHA supplementation alone and in combination with carboplatin significantly reduced OC growth in a high-grade serous OC patient-derived xenograft mouse model. Carboplatin administered intraperitoneally significantly reduced tumor growth in DHA-fed mice compared to mice on the control diet. Intravenous carboplatin administration in combination with DHA reduced tumor growth similarly to carboplatin or DHA monotherapies. The DHA-induced reduction in tumor growth in this model was associated with increased tumor necrosis and improved survival. As such, our findings provide a strong rationale to move to clinical trials that will determine whether DHA supplementation enhances the efficacy and tolerance of cytotoxic chemotherapy in patients with OC.

Docosahexaenoic Acid in the Inhibition of Tumor Cell Growth in Preclinical Models of Ovarian Cancer

2021 ◽  
pp. 1-15
Author(s):  
Olena Bilyk ◽  
Bahareh Hamedi ◽  
Indrani Dutta ◽  
Marnie Newell ◽  
Amirali B. Bukhari ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Growth ◽  
Docosahexaenoic Acid ◽  
Tumor Cell ◽  
Tumor Cell Growth ◽  
Preclinical Models

scholarly journals DGAT1 Expression Promotes Ovarian Cancer Progression and Is Associated with Poor Prognosis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Leilei Xia ◽  
Ye Wang ◽  
Shengyun Cai ◽  
Mingjuan Xu
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Rapid Development ◽  
Lipid Synthesis ◽  
Cancer Staging ◽  
The Cancer Genome Atlas ◽  
Ovarian Cancer Cells ◽  
Gynecological Malignancy

Background. Ovarian cancer is the most fatal gynecological malignancy. Owing to its insidious onset, rapid development, and poor prognosis, ovarian cancer is the fifth most common cause of death in women. Although immunotherapy-related drugs, such as Olaparib, can alleviate ovarian cancer progression, there are no remarkable breakthroughs for its effective treatment. It is considered that the transformation of normal cells to cancerous ones involves “recoding” of certain metabolic pathways. Diacylglycerol O-acyltransferase 1 (DGAT1) can synthesize triglycerides by transferring acyl-CoA to diacylglycerol, which plays a key role in lipid synthesis. However, the role of DGAT1 in ovarian cancer is not yet elucidated. Materials and Methods. We analyzed the correlation between DGAT1 and ovarian cancer staging, grading, vascular invasion, and prognosis by collating the information of ovarian cancer specimens from The Cancer Genome Atlas (TCGA) database. Furthermore, the effects of DGAT1 expression on proliferation, migration, invasion, and tumor growth were studied using ovarian cancer cell lines. GSEA was used to analyze the KEGG pathways and biological function enriched because of DGAT1 expression in ovarian cancer. Results. The expression of DGAT1 was elevated in advanced ( p = 0.0432 ), poorly differentiated ( p = 0.0148 ), and vascular invaded ( p = 0.0002 ) ovarian cancer specimens. Prognosis among patients with high expression of DGAT1 was poor. After DGAT1 expression was interfered, proliferation, migration, invasion, colony forming, and tumor growth of ovarian cancer cells were inhibited. In addition, GSEA showed that DGAT1 may be involved in the immune process. Conclusion. DGAT1 expression is associated with the clinical phenotype of ovarian cancer. We suggest that DGAT1 has potential implications in the treatment of ovarian cancer.

scholarly journals Targeting Ovarian Carcinoma with TSP-1:CD47 Antagonist TAX2 Activates Anti-Tumor Immunity

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 5019
Author(s):  
Albin Jeanne ◽  
Thomas Sarazin ◽  
Magalie Charlé ◽  
Catherine Moali ◽  
Caroline Fichel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Cyclic Peptide ◽  
Drug Candidate ◽  
Preclinical Models ◽  
Cell Immunity ◽  
Anti Cancer ◽  
Clinical Data Mining ◽  
Favorable Safety

TAX2 peptide is a cyclic peptide that acts as an orthosteric antagonist for thrombospondin-1 (TSP-1) interaction with CD47. TAX2 was first described for its anti-angiogenic activities and showed anti-cancer efficacy in numerous preclinical models. Here, we aimed at providing an extensive molecular characterization of TAX2 mode of action, while evaluating its potential in ovarian cancer therapy. Multidisciplinary approaches were used to qualify a TAX2 drug candidate in terms of stability, solubility and potency. Then, efficacy studies, together with benchmark experiments, were performed in relevant mouse models of ovarian carcinoma. TAX2 peptide appears to be stable and soluble in clinically relevant solvents, while displaying a favorable safety profile. Moreover, clinical data mining allowed for the identification of TSP-1 as a relevant pharmacological target in ovarian cancer. In mice, TAX2 therapy inhibits ovarian tumor growth and metastatic dissemination, while activating anti-cancer adaptive immunity. Interestingly, TAX2 also synergizes when administered in combination with anti-PD-1 immune checkpoint inhibitiors. Altogether, our data expose TAX2 as an optimized candidate with advanced preclinical characterization. Using relevant syngeneic ovarian carcinoma models, we highlighted TAX2’s ability to convert poorly immunogenic tumors into ones displaying effective anti-tumor T-cell immunity.

The emerging roles of extracellular vesicles in ovarian cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Yin-xue Wang ◽  
Yi-xiang Wang ◽  
Yi-ke Li ◽  
Shi-yan Tu ◽  
Yi-qing Wang
Keyword(s):  
Ovarian Cancer ◽  
Extracellular Vesicles ◽  
Large Scale ◽  
Current Treatment ◽  
Detection Methods ◽  
Drug Resistant ◽  
Apoptotic Bodies ◽  
Biological Mechanisms ◽  
Gynecological Malignancy ◽  
Resistance To Chemotherapy

: Ovarian cancer (OC) is one of the deadliest gynecological malignancy. Epithelial ovarian cancer (EOC) is its most common form. OC has both a poor prognosis and a high mortality rate due to the difficulties of early diagnosis, the limitation of current treatment and resistance to chemotherapy. Extracellular vesicles is a heterogeneous group of cellderived submicron vesicles which can be detected in body fluids, and it can be classified into three main types including exosomes, micro-vesicles, and apoptotic bodies. Cancer cells can produce more EVs than healthy cells. Moreover, the contents of these EVs have been found distinct from each other. It has been considered that EVs shedding from tumor cells may be implicated in clinical applications. Such as a tool for tumor diagnosis, prognosis and potential treatment of certain cancers. In this review, we provide a brief description of EVs in diagnosis, prognosis, treatment, drug-resistant of OC. Cancer-related EVs show powerful influences on tumors by various biological mechanisms. However, the contents mentioned above remain in the laboratory stage and there is a lack of large-scale clinical trials, and the maturity of the purification and detection methods is a constraint. In addition, amplification of oncogenes on ecDNA is remarkably prevalent in cancer, it may be possible that ecDNA can be encapsulated in EVs and thus detected by us. In summary, much more research on EVs needs to be perform to reveal breakthroughs in OC and to accelerate the process of its application on clinic.

scholarly journals Targeting galectin-3 with a high-affinity antibody for inhibition of high-grade serous ovarian cancer and other MUC16/CA-125-expressing malignancies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marina Stasenko ◽  
Evan Smith ◽  
Oladapo Yeku ◽  
Kay J. Park ◽  
Ian Laster ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Therapeutics ◽  
Ca 125 ◽  
Ovarian Cancer Cells ◽  
Carbohydrate Binding ◽  
Matrigel Invasion ◽  
Galectin 3

AbstractThe lectin, galectin-3 (Gal3), has been implicated in a variety of inflammatory and oncogenic processes, including tumor growth, invasion, and metastasis. The interactions of Gal3 and MUC16 represent a potential targetable pathway for the treatment of MUC16-expressing malignancies. We found that the silencing of Gal3 in MUC16-expressing breast and ovarian cancer cells in vitro inhibited tumor cell invasion and led to attenuated tumor growth in murine models. We therefore developed an inhibitory murine monoclonal anti–Gal3 carbohydrate-binding domain antibody, 14D11, which bound human and mouse Gal3 but did not bind human Galectins-1, -7, -8 or -9. Competition studies and a docking model suggest that the 14D11 antibody competes with lactose for the carbohydrate binding pocket of Gal3. In MUC16-expressing cancer cells, 14D11 treatment blocked AKT and ERK1/2 phosphorylation, and led to inhibition of cancer cell Matrigel invasion. Finally, in experimental animal tumor models, 14D11 treatment led to prolongation of overall survival in animals bearing flank tumors, and retarded lung specific metastatic growth by MUC16 expressing breast cancer cells. Our results provide evidence that antibody based Gal3 blockade may be a viable therapeutic strategy in patients with MUC16-expressing tumors, supporting further development of human blocking antibodies against Gal3 as potential cancer therapeutics.

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