scholarly journals Emerging and Evolving Ovarian Cancer Animal Models

2015 ◽  
Vol 8s1 ◽  
pp. CGM.S21221 ◽  
Author(s):  
Alexander S. Bobbs ◽  
Jennifer M. Cole ◽  
Karen D. Cowden Dahl
Keyword(s):  
Ovarian Cancer ◽  
Animal Models ◽  
Mouse Models ◽  
Immune Cell ◽  
Treatment Options ◽  
The United States ◽  
Genetically Engineered ◽  
Response To Therapy ◽  
Gynecological Malignancy ◽  
Immunocompetent Mice

Ovarian cancer (OC) is the leading cause of death from a gynecological malignancy in the United States. By the time a woman is diagnosed with OC, the tumor has usually metastasized. Mouse models that are used to recapitulate different aspects of human OC have been evolving for nearly 40 years. Xenograft studies in immunocompromised and immunocompetent mice have enhanced our knowledge of metastasis and immune cell involvement in cancer. Patient-derived xenografts (PDXs) can accurately reflect metastasis, response to therapy, and diverse genetics found in patients. Additionally, multiple genetically engineered mouse models have increased our understanding of possible tissues of origin for OC and what role individual mutations play in establishing ovarian tumors. Many of these models are used to test novel therapeutics. As no single model perfectly copies the human disease, we can use a variety of OC animal models in hypothesis testing that will lead to novel treatment options. The goal of this review is to provide an overview of the utility of different mouse models in the study of OC and their suitability for cancer research.

scholarly journals Profiling the intratumoral immune landscapes of primary and syngeneic Kras-driven sarcoma mouse models

2020 ◽  
Author(s):  
Wade R. Gutierrez ◽  
Amanda Scherer ◽  
Gavin R. McGivney ◽  
Vickie Knepper-Adrian ◽  
Emily A. Laverty ◽  
...  
Keyword(s):  
T Cell ◽  
Mouse Models ◽  
Primary Tumor ◽  
Immune Cell ◽  
Genetically Engineered ◽  
Cell Transplant ◽  
Tumor Models ◽  
Primary Tumors ◽  
Cell Composition ◽  
Immunocompetent Mice

ABSTRACTThe introduction of immunotherapy has revolutionized cancer treatment and fueled interest in the immune cell composition of preclinical tumor models. Both genetically-engineered mouse models and syngeneic cell transplant approaches use immunocompetent mice to study mechanisms driving immunotherapy response and resistance. Due to their rapid and reproducible nature, there has been an expanded interest in developing new syngeneic tools from established primary tumor models. However, there are few analyses directly comparing the immune profiles of primary models with their derived syngeneic counterparts. Here we report comprehensive immunophenotyping of primary tumors from two well-established sarcoma models and four syngeneic allografts derived from these models. We observed that cell lines derived from the same type of genetically engineered primary tumor form allografts with significantly different levels of immune infiltration and intratumoral immune cell composition. Most notable are the differences in the T cell compartment of the syngeneic models, including CD4+ T cell, CD8+ T cell, and regulatory T cell populations – each of which have well-documented roles in tumor response to immunotherapy. Our findings highlight the importance of thorough characterization of syngeneic models prior to their use in preclinical studies in order to maintain scientific rigor and to increase the translatability of findings from bench to bedside.

scholarly journals Animal models of colorectal peritoneal metastasis

2016 ◽  
Vol 1 (1) ◽  
pp. 23-43 ◽  
Author(s):  
Félix Gremonprez ◽  
Wouter Willaert ◽  
Wim Ceelen
Keyword(s):  
Colorectal Cancer ◽  
Animal Models ◽  
Peritoneal Carcinomatosis ◽  
Peritoneal Metastasis ◽  
Treatment Options ◽  
Genetically Engineered ◽  
Preclinical Research ◽  
Novel Treatment ◽  
Genetically Engineered Mice ◽  
Wide Range

AbstractColorectal cancer remains an important cause of mortality worldwide. The presence of peritoneal carcinomatosis (PC) causes significant symptoms and is notoriously difficult to treat. Therefore, informative preclinical research into the mechanisms and possible novel treatment options of colorectal PC is essential in order to improve the prognostic outlook in these patients. Several syngeneic and xenograft animal models of colorectal PC were established, studying a wide range of experimental procedures and substances. Regrettably, more sophisticated models such as those giving rise to spontaneous PC or involving genetically engineered mice are lacking. Here, we provide an overview of all reported colorectal PC animal models and briefly discuss their use, strengths, and limitations.

scholarly journals Experimental models in the study of pathogenesis and the development of treatments for ovarian cancer (systematic review)

2021 ◽  
Vol 67 (4) ◽  
pp. 463-473
Author(s):  
Galina ZHUKOVA ◽  
Ekasterina Verenikina ◽  
Tatiana Protasova ◽  
Daria Yakubova ◽  
Anastasia Volkova
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Animal Models ◽  
Web Of Science ◽  
Ex Vivo ◽  
Primary Cultures ◽  
Genetically Engineered ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Immunodeficient Mice

A systematic review of modern methods of experimental study of ovarian cancer using traditional (immunocompetent, genetically engineered and immunodeficient) and non-traditional (that don’t belong to the mammals) animal models,established and primary cultures of human ovarian cancer, including three-dimensional organotypic spheroids (3D- models ex vivo) is presented. The prospects of the considered models for studying of the pathogenesis of various molecular-genetic and histological variants of ovarian cancer, as well as for developing methods of personalized treatment, are discussed. The limitations of modern animal models are indicated. The greatest attention is paid to studies on immunodeficient animals using xenografts based on established cultures of human ovarian cancer cells and on tumor tissue obtained directly from the patients (patient derived xenografts, PDX). The questions of various variants of xenograft transplantation with an emphasis on the problems of orthotopic transplantation of human ovarian cancer into immunodeficient mice and the relevance of methods for local humanization in heterotopic transplantation are considered. The most promising, from the point of the author’s view, approaches to studying the effectiveness of drug therapy for ovarian cancer in immunodeficient animal models are outlined. To prepare a systematic review, a literature search was carried out on the Scopus, Web of Science, Med Line, PubMed, Cyber Leninka, RSCI databases. The analysis used literature sources indexed in the Scopus and Web of Science databases (97%) and the RSCI. More than 60% of the works amount has been published over the past 5 years.

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.

Modeling the impact of genetic heterogeneity on immunotherapy

2020 ◽  
Vol 12 (571) ◽  
pp. eabf7104
Author(s):  
Ioannis Zervantonakis
Keyword(s):  
Ovarian Cancer ◽  
Mouse Models ◽  
Genetic Heterogeneity ◽  
Genetically Engineered ◽  
Genetically Engineered Mouse Models ◽  
The Impact

A panel of genetically engineered mouse models recapitulates genotype-driven responses to immunotherapy and uncovers a driver of immunotherapy resistance in ovarian cancer.

scholarly journals Cyclooxygenase-1 Is Overexpressed in Multiple Genetically Engineered Mouse Models of Epithelial Ovarian Cancer

2006 ◽  
Vol 66 (5) ◽  
pp. 2527-2531 ◽  
Author(s):  
Takiko Daikoku ◽  
Susanne Tranguch ◽  
Irina N. Trofimova ◽  
Daniela M. Dinulescu ◽  
Tyler Jacks ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Mouse Models ◽  
Genetically Engineered ◽  
Genetically Engineered Mouse Models ◽  
Cyclooxygenase 1

scholarly journals Regulation of Survivin Isoform Expression by GLI Proteins in Ovarian Cancer

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 128 ◽  
Author(s):  
Diana Trnski ◽  
Maja Gregorić ◽  
Sonja Levanat ◽  
Petar Ozretić ◽  
Nikolina Rinčić ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Line ◽  
Treatment Options ◽  
Clinical Samples ◽  
Knock Out ◽  
Gynecological Malignancy ◽  
Gli Proteins ◽  
Apoptosis Protein ◽  
Isoform Expression

Ovarian cancer (OC) is the most lethal female gynecological malignancy, mostly due to diagnosis in late stages when treatment options are limited. Hedgehog-GLI (HH-GLI) signaling is a major developmental pathway involved in organogenesis and stem cell maintenance, and is activated in OC. One of its targets is survivin (BIRC5), an inhibitor of apoptosis protein (IAP) that plays a role in multiple processes, including proliferation and cell survival. We wanted to investigate the role of different GLI proteins in the regulation of survivin isoform expression (WT, 2α, 2B, 3B, and Δex3) in the SKOV-3 OC cell line. We demonstrated that survivin isoforms are downregulated in GLI1 and GLI2 knock-out cell lines, but not in the GLI3 knock-out. Treatment of GLI1 knock-out cells with GANT-61 shows an additional inhibitory effect on several isoforms. Additionally, we examined the expression of survivin isoforms in OC samples and the potential role of BIRC5 polymorphisms in isoform expression. Clinical samples showed the same pattern of survivin isoform expression as in the cell line, and several BIRC5 polymorphisms showed the correlation with isoform expression. Our results showed that survivin isoforms are regulated both by different GLI proteins and BIRC5 polymorphisms in OC.

scholarly journals siRNA-Conjugated Nanoparticles to Treat Ovarian Cancer

2019 ◽  
Vol 24 (2) ◽  
pp. 137-150 ◽  
Author(s):  
Christopher Halbur ◽  
Niharika Choudhury ◽  
Michael Chen ◽  
Jun Hyuk Kim ◽  
Eun Ji Chung
Keyword(s):  
Ovarian Cancer ◽  
Targeted Delivery ◽  
Target Genes ◽  
Treatment Options ◽  
Chemotherapy Resistance ◽  
The United States ◽  
Tumor Burden ◽  
Ovarian Cancer Cells ◽  
Reduce Tumor Burden ◽  
Sirna Therapy

Ovarian cancer is the fifth-most lethal cancer among women due to a lack of early detection and late-stage treatment options, and it is responsible for more than 14,000 deaths each year in the United States. Recently, there have been advances in RNA interference therapy, specifically with small interfering RNA (siRNA), to reduce tumor burden for ovarian cancer via gene down-regulation. However, delivery of siRNA poses its own challenges, as siRNA is unstable in circulation, is unable to be effectively internalized by cells, and may cause toxicity in off-target sites. To address such challenges, nanoparticle carriers have emerged as delivery platforms for the biocompatible, targeted delivery of siRNA-based therapies. Several preclinical studies have shown the promising effects of siRNA therapy to reduce chemotherapy resistance and proliferation of ovarian cancer cells. This review evaluates the recent advances, clinical applications, and future potential of nanoparticle-mediated delivery of siRNA therapeutics to target genes implicated in ovarian cancer.

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