Zebrafish: The Key for Cancer Treatment

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (31 August 2017) | Viewed by 44134

Special Issue Editor


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Guest Editor
Department of Zoology, Genetics and Physical Anthropology, University of Santiago de Compostela, Santiago de Compostela, 15705 Galicia, Spain
Interests: zebrafish; Danio rerio; animal models for human disease; xenograft of tumor cells; toxicity
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Special Issue Information

Dear Colleagues,

Zebrafish has been used since the early 1970s in Oregon as a model organism for vertebrate development and gene function. Over the past few years, zebrafish has emerged as a cancer model that complements the murine system. This model was discovered in cancer research with cancer currently being the second cause of death worldwide. It has been increasingly used in subsequent years due to the exponential growth of cancer, especially in developed countries. By virtue of its experimental swiftness, low cost maintenance and high-throughput advantages against the murine model, the zebrafish has had a high impact on research.

Covering areas ranging from biochemistry or genetics, to toxicology or xenotransplantation, zebrafish is a useful tool to discover some of the most important underlying mechanisms of cancer proliferation, migration and metastasis. Using this small fish, researchers from all over the world are able to gather information in a very efficient way to fight against this heterogeneous disease.

In this Special Issue, we would like to invite submissions of original research or review articles on any topic related to “Zebrafish: The Key for Cancer Treatment”. We thereby hope to gather knowledge to find critical steps for cancer treatment using this model organism. We look forward to receiving your contributions.

Dr. Laura Sánchez
Guest Editor

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Keywords

  • zebrafish
  • cancer
  • model organism
  • xenograft
  • screening
  • high throughput

Published Papers (6 papers)

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Research

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Article
The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome
by Ludivine Renaud, Willian A. da Silveira, E. Starr Hazard, Jonathan Simpson, Silvia Falcinelli, Dongjun Chung, Oliana Carnevali and Gary Hardiman
Genes 2017, 8(10), 269; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8100269 - 13 Oct 2017
Cited by 25 | Viewed by 6518
Abstract
Ubiquitous exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs (miRNAs), are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly [...] Read more.
Ubiquitous exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs (miRNAs), are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly characterized. Zebrafish represents an excellent model to study cancer as the organism develops a disease that resembles human cancer. Using zebrafish as a systems toxicology model, we hypothesized that chronic BPA-exposure impacts the miRNome in adult zebrafish and establishes an epigenome more susceptible to cancer development. After a 3 week exposure to 100 nM BPA, RNA from the liver was extracted to perform high throughput mRNA and miRNA sequencing. Differential expression (DE) analyses comparing BPA-exposed to control specimens were performed using established bioinformatics pipelines. In the BPA-exposed liver, 6188 mRNAs and 15 miRNAs were differently expressed (q ≤ 0.1). By analyzing human orthologs of the DE zebrafish genes, signatures associated with non-alcoholic fatty liver disease (NAFLD), oxidative phosphorylation, mitochondrial dysfunction and cell cycle were uncovered. Chronic exposure to BPA has a significant impact on the liver miRNome and transcriptome in adult zebrafish with the potential to cause adverse health outcomes including cancer. Full article
(This article belongs to the Special Issue Zebrafish: The Key for Cancer Treatment)
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2738 KiB  
Article
RECQ1 Helicase Silencing Decreases the Tumour Growth Rate of U87 Glioblastoma Cell Xenografts in Zebrafish Embryos
by Miloš Vittori, Barbara Breznik, Katja Hrovat, Saša Kenig and Tamara T. Lah
Genes 2017, 8(9), 222; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8090222 - 06 Sep 2017
Cited by 12 | Viewed by 5222
Abstract
RECQ1 helicase has multiple roles in DNA replication, including restoration of the replication fork and DNA repair, and plays an important role in tumour progression. Its expression is highly elevated in glioblastoma as compared to healthy brain tissue. We studied the effects of [...] Read more.
RECQ1 helicase has multiple roles in DNA replication, including restoration of the replication fork and DNA repair, and plays an important role in tumour progression. Its expression is highly elevated in glioblastoma as compared to healthy brain tissue. We studied the effects of small hairpin RNA (shRNA)-induced silencing of RECQ1 helicase on the increase in cell number and the invasion of U87 glioblastoma cells. RECQ1 silencing reduced the rate of increase in the number of U87 cells by 30%. This corresponded with a 40% reduction of the percentage of cells in the G2 phase of the cell cycle, and an accumulation of cells in the G1 phase. These effects were confirmed in vivo, in the brain of zebrafish (Danio rerio) embryos, by implanting DsRed-labelled RECQ1 helicase-silenced and control U87 cells. The growth of resulting tumours was quantified by monitoring the increase in xenograft fluorescence intensity during a three-day period with fluorescence microscopy. The reduced rate of tumour growth, by approximately 30% in RECQ1 helicase-silenced cells, was in line with in vitro measurements of the increase in cell number upon RECQ1 helicase silencing. However, RECQ1 helicase silencing did not affect invasive behaviour of U87 cells in the zebrafish brain. This is the first in vivo confirmation that RECQ1 helicase is a promising molecular target in the treatment of glioblastoma. Full article
(This article belongs to the Special Issue Zebrafish: The Key for Cancer Treatment)
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Review

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Review
The Potential of Zebrafish as a Model Organism for Improving the Translation of Genetic Anticancer Nanomedicines
by C Gutiérrez-Lovera, AJ Vázquez-Ríos, J Guerra-Varela, L Sánchez and M De la Fuente
Genes 2017, 8(12), 349; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8120349 - 28 Nov 2017
Cited by 27 | Viewed by 8409
Abstract
In the last few decades, the field of nanomedicine applied to cancer has revolutionized cancer treatment: several nanoformulations have already reached the market and are routinely being used in the clinical practice. In the case of genetic nanomedicines, i.e., designed to deliver gene [...] Read more.
In the last few decades, the field of nanomedicine applied to cancer has revolutionized cancer treatment: several nanoformulations have already reached the market and are routinely being used in the clinical practice. In the case of genetic nanomedicines, i.e., designed to deliver gene therapies to cancer cells for therapeutic purposes, advances have been less impressive. This is because of the many barriers that limit the access of the therapeutic nucleic acids to their target site, and the lack of models that would allow for an improvement in the understanding of how nanocarriers can be tailored to overcome them. Zebrafish has important advantages as a model species for the study of anticancer therapies, and have a lot to offer regarding the rational development of efficient delivery of genetic nanomedicines, and hence increasing the chances of their successful translation. This review aims to provide an overview of the recent advances in the development of genetic anticancer nanomedicines, and of the zebrafish models that stand as promising tools to shed light on their mechanisms of action and overall potential in oncology. Full article
(This article belongs to the Special Issue Zebrafish: The Key for Cancer Treatment)
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Review
Zebrafish in Translational Cancer Research: Insight into Leukemia, Melanoma, Glioma and Endocrine Tumor Biology
by Aurora Irene Idilli, Francesca Precazzini, Maria Caterina Mione and Viviana Anelli
Genes 2017, 8(9), 236; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8090236 - 20 Sep 2017
Cited by 28 | Viewed by 8512
Abstract
Over the past 15 years, zebrafish have emerged as a powerful tool for studying human cancers. Transgenic techniques have been employed to model different types of tumors, including leukemia, melanoma, glioblastoma and endocrine tumors. These models present histopathological and molecular conservation with their [...] Read more.
Over the past 15 years, zebrafish have emerged as a powerful tool for studying human cancers. Transgenic techniques have been employed to model different types of tumors, including leukemia, melanoma, glioblastoma and endocrine tumors. These models present histopathological and molecular conservation with their human cancer counterparts and have been fundamental for understanding mechanisms of tumor initiation and progression. Moreover, xenotransplantation of human cancer cells in embryos or adult zebrafish offers the advantage of studying the behavior of human cancer cells in a live organism. Chemical-genetic screens using zebrafish embryos have uncovered novel druggable pathways and new therapeutic strategies, some of which are now tested in clinical trials. In this review, we will report on recent advances in using zebrafish as a model in cancer studies—with specific focus on four cancer types—where zebrafish has contributed to novel discoveries or approaches to novel therapies. Full article
(This article belongs to the Special Issue Zebrafish: The Key for Cancer Treatment)
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Review
Emerging Estrogenic Pollutants in the Aquatic Environment and Breast Cancer
by Sylvain Lecomte, Denis Habauzit, Thierry D. Charlier and Farzad Pakdel
Genes 2017, 8(9), 229; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8090229 - 15 Sep 2017
Cited by 62 | Viewed by 8254
Abstract
The number and amount of man-made chemicals present in the aquatic environment has increased considerably over the past 50 years. Among these contaminants, endocrine-disrupting chemicals (EDCs) represent a significant proportion. This family of compounds interferes with normal hormonal processes through multiple molecular pathways. [...] Read more.
The number and amount of man-made chemicals present in the aquatic environment has increased considerably over the past 50 years. Among these contaminants, endocrine-disrupting chemicals (EDCs) represent a significant proportion. This family of compounds interferes with normal hormonal processes through multiple molecular pathways. They represent a potential risk for human and wildlife as they are suspected to be involved in the development of diseases including, but not limited to, reprotoxicity, metabolic disorders, and cancers. More precisely, several studies have suggested that the increase of breast cancers in industrialized countries is linked to exposure to EDCs, particularly estrogen-like compounds. Estrogen receptors alpha (ERα) and beta (ERβ) are the two main transducers of estrogen action and therefore important targets for these estrogen-like endocrine disrupters. More than 70% of human breast cancers are ERα-positive and estrogen-dependent, and their development and growth are not only influenced by endogenous estrogens but also likely by environmental estrogen-like endocrine disrupters. It is, therefore, of major importance to characterize the potential estrogenic activity from contaminated surface water and identify the molecules responsible for the hormonal effects. This information will help us understand how environmental contaminants can potentially impact the development of breast cancer and allow us to fix a maximal limit to the concentration of estrogen-like compounds that should be found in the environment. The aim of this review is to provide an overview of emerging estrogen-like compounds in the environment, sum up studies demonstrating their direct or indirect interactions with ERs, and link their presence to the development of breast cancer. Finally, we emphasize the use of in vitro and in vivo methods based on the zebrafish model to identify and characterize environmental estrogens. Full article
(This article belongs to the Special Issue Zebrafish: The Key for Cancer Treatment)
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Review
Zebrafish Xenograft: An Evolutionary Experiment in Tumour Biology
by Rachael A. Wyatt, Nhu P. V. Trieu and Bryan D. Crawford
Genes 2017, 8(9), 220; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8090220 - 05 Sep 2017
Cited by 14 | Viewed by 5998
Abstract
Though the cancer research community has used mouse xenografts for decades more than zebrafish xenografts, zebrafish have much to offer: they are cheap, easy to work with, and the embryonic model is relatively easy to use in high-throughput assays. Zebrafish can be imaged [...] Read more.
Though the cancer research community has used mouse xenografts for decades more than zebrafish xenografts, zebrafish have much to offer: they are cheap, easy to work with, and the embryonic model is relatively easy to use in high-throughput assays. Zebrafish can be imaged live, allowing us to observe cellular and molecular processes in vivo in real time. Opponents dismiss the zebrafish model due to the evolutionary distance between zebrafish and humans, as compared to mice, but proponents argue for the zebrafish xenograft’s superiority to cell culture systems and its advantages in imaging. This review places the zebrafish xenograft in the context of current views on cancer and gives an overview of how several aspects of this evolutionary disease can be addressed in the zebrafish model. Zebrafish are missing homologs of some human proteins and (of particular interest) several members of the matrix metalloproteinase (MMP) family of proteases, which are known for their importance in tumour biology. This review draws attention to the implicit evolutionary experiment taking place when the molecular ecology of the xenograft host is significantly different than that of the donor. Full article
(This article belongs to the Special Issue Zebrafish: The Key for Cancer Treatment)
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