Animal Models to Study Cancer and Its Microenvironment

Mendes, Nuno; Carvalho, Patrícia Dias; Martins, Francisco Vitorino; Mendonça, Susana; Malheiro, Ana Rita; Ribeiro, Andreia; Carvalho, Joana; Velho, Sérgia

doi:10.1007/978-3-030-34025-4_20

Cited by 25 publications

(19 citation statements)

References 68 publications

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“…Paeonol had no side effects on the structure of liver and kidney tissues, suggesting that paeonol could be significantly better than cisplatin in terms of adverse reaction, which may be due to the antiinflammatory effects of paeonol (Zhang L. et al, 2019). It has been increasingly recognized that tumor microenvironment plays an important role in carcinogenesis (Mendes et al, 2020). Inflammation often exists in tumor microenvironment and is induced by inflammatory mediators produced by the tumor, stroma, and infiltrating cells.…”

Section: Discussionmentioning

confidence: 99%

Paeonol Suppresses Proliferation and Motility of Non-Small-Cell Lung Cancer Cells by Disrupting STAT3/NF-κB Signaling

Zhang

Chen

et al. 2020

Front. Pharmacol.

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Background: Targeting inflammatory microenvironment is a promising anti-tumor strategy. Paeonol is a phenolic compound with effective anti-inflammatory and anti-tumor properties. However, the effects of paeonol on non-small cell carcinoma (NSCLC) have not been fully investigated. Here, we evaluated the effects of paeonol on proliferation and metastasis of NSCLC and elucidated the underlying mechanisms.Methods: The effects of paeonol on inflammatory cytokines were determined by cell proliferation and ELISA assays. Assays of wound healing, single cell migration and perforation invasion were used to evaluate migration and invasion of NSCLC cells. Expression of marker proteins in epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) family enzymes were detected by Western blot assays. Nude mouse A549 cells transplantation tumor model was used to study the anti-lung cancer effects of paeonol in vivo. TUNEL stanining were used to detect the apoptosis of tumor cells in A549 lung cancer mice, and Ki67 analysis was used to detect the proliferation of tumor cells in A549 lung cancer mice. Immunohistochemistry was used to detect the effects of paeonol on signaling molecules in tumor tissues.Results: Paeonol inhibited A549 cancer cell migration and invasion in vitro. Paeonol inhibited secreaion of inflammatory cytokines in A549 cells, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and transforming growth factor (TGF)-β. Paeonol altered the expression of marker proteins involved in EMT and MMP family enzymes. In addition, paeonol inhibited the transcriptional activity of nuclear factor-κB (NF-κB) and phosphorylation of signal transducers and activators of transcription 3 (STAT3). Paeonol inhibited the growth of A549 cells transplanted tumors in nude mice.Conclusion: Paeonol potently inhibited NSCLC cell growth, migration and invasion associated with disruption of STAT3 and NF-κB pathways, suggesting that it could be a promising anti-metastatic candidate for tumor chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Paeonol Suppresses Proliferation and Motility of Non-Small-Cell Lung Cancer Cells by Disrupting STAT3/NF-κB Signaling

Zhang

Chen

et al. 2020

Front. Pharmacol.

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“…Bioprinting technology is particularly suitable for the creation of tumor models, as the high precision and reproducibility can recapitulate the tumor microenvironment (TME) [ 7 , 8 ]. In most animal models, human tumors are embedded in a xenogenic animal environment [ 9 ]. This arrangement may produce results with limited relevance to human pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

Bioprinted Cancer Model of Neuroblastoma in a Renal Microenvironment as an Efficiently Applicable Drug Testing Platform

Berg

Arlt

et al. 2021

IJMS

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Development of new anticancer drugs with currently available animal models is hampered by the fact that human cancer cells are embedded in an animal-derived environment. Neuroblastoma is the most common extracranial solid malignancy of childhood. Major obstacles include managing chemotherapy-resistant relapses and resistance to induction therapy, leading to early death in very-high-risk patients. Here, we present a three-dimensional (3D) model for neuroblastoma composed of IMR-32 cells with amplified genes of the myelocytomatosis viral related oncogene MYCN and the anaplastic lymphoma kinase (ALK) in a renal environment of exclusively human origin, made of human embryonic kidney 293 cells and primary human kidney fibroblasts. The model was produced with two pneumatic extrusion printheads using a commercially available bioprinter. Two drugs were exemplarily tested in this model: While the histone deacetylase inhibitor panobinostat selectively killed the cancer cells by apoptosis induction but did not affect renal cells in the therapeutically effective concentration range, the peptidyl nucleoside antibiotic blasticidin induced cell death in both cell types. Importantly, differences in sensitivity between two-dimensional (2D) and 3D cultures were cell-type specific, making the therapeutic window broader in the bioprinted model and demonstrating the value of studying anticancer drugs in human 3D models. Altogether, this cancer model allows testing cytotoxicity and tumor selectivity of new anticancer drugs, and the open scaffold design enables the free exchange of tumor and microenvironment by any cell type.

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“…At present, there are four commonly used methods to construct mouse cancer model: chemically induced model, cell line-derived xenograft (CDX) model, patientderived xenograft (PDX) model and genetically engineered mouse model (GEMM). 6 The chemical induction model refers to the model of experimental tumor induced by chemical carcinogens, which has the advantage of imitating the occurrence of human cancer from the beginning of the carcinogenic process. 7 But the main disadvantage of this method is that it takes 30-50 weeks to form a tumor after using carcinogens.…”

Section: Mouse Modelmentioning

confidence: 99%

Application of Animal Models in Cancer Research: Recent Progress and Future Prospects

Wen-ling

Wang

et al. 2021

CMAR

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Animal models refers to the animal experimental objects and related materials that can simulate human body established in medical research. As the second-largest disease in terms of morbidity and mortality after cardiovascular disease, cancer has always been the focus of human attention all over the world, which makes it a research hotspot in the medical field. At the same time, more and more animal models have been constructed and used in cancer research. With the deepening of research, the construction methods of cancer animal models are becoming more and more diverse, including chemical induction, xenotransplantation, gene programming, and so on. In recent years, patient-derived xenotransplantation (PDX) model has become a research hotspot because it can retain the microenvironment of the primary tumor and the basic characteristics of cells. Animal models can be used not only to study the biochemical and physiological processes of the occurrence and development of cancer in objects but also for the screening of cancer drugs and the exploration of gene therapy. In this paper, several main tumor animal models and the application progress of animal models in tumor research are systematically reviewed. Finally, combined with the latest progress and development trend in this field, the future research of tumor animal model was prospected.

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Animal Models to Study Cancer and Its Microenvironment

Cited by 25 publications

References 68 publications

Paeonol Suppresses Proliferation and Motility of Non-Small-Cell Lung Cancer Cells by Disrupting STAT3/NF-κB Signaling

Paeonol Suppresses Proliferation and Motility of Non-Small-Cell Lung Cancer Cells by Disrupting STAT3/NF-κB Signaling

Bioprinted Cancer Model of Neuroblastoma in a Renal Microenvironment as an Efficiently Applicable Drug Testing Platform

Application of Animal Models in Cancer Research: Recent Progress and Future Prospects

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