Animal models of disease: Pre-clinical animal models of cancer and their applications and utility in drug discovery

Ruggeri, Bruce; Camp, Faye; Miknyoczki, Sheila

doi:10.1016/j.bcp.2013.06.020

Cited by 290 publications

(240 citation statements)

References 84 publications

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“…Moreover, the invasive ability was also significantly attenuated in the calcitriol-treated group, as determined by cellular invasion assays and an orthotopic tumor model. An orthotopic tumor model has been reported to increase the invasive and metastatic potential demonstrated by tumor cell lines following injection into their tissue of origin compared with subcutaneous tumor, which is an unrealistic growth location (34,35). The transformation of an epithelial cell into a mesenchymal cell has been reported to be relevant to the invasive characteristics of epithelial tumors, including esophageal cancer (20,36).…”

Section: Discussionmentioning

confidence: 99%

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

Chen

Hsieh

et al. 2015

Molecular Cancer Therapeutics

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The aim of this study was to highlight the role of 1a,25-dihydroxyvitamin D3 (calcitriol) in esophageal squamous cell carcinoma (SCC). The human esophageal SCC cell lines CE81T and TE2 were selected for cellular and animal experiments to investigate the changes in tumor behavior after calcitriol supplementation and the underlying mechanisms. Moreover, we evaluated the relationship between calcitriol supplementation, myeloid-derived suppressor cell (MDSC) recruitment, IL6 levels, and tumor progression by a 4-nitroquinoline 1-oxide (4-NQO)-induced esophageal tumor animal model. In this study, we demonstrated that calcitriol supplementation inhibited aggressive tumor behavior both in vitro and in vivo. The underlying changes included increased cell death, a lower degree of epithelial-mesenchymal transition, and inhibited IL6 signaling. In the 4-NQOinduced esophageal tumor animal model, increased IL6 and MDSC recruitment were linked with invasive esophageal tumors. Supplementation with calcitriol attenuated the level of IL6, the induction of MDSCs, and the incidence of 4-NQO-induced invasive tumors. Moreover, the IL6-induced changes in C57 mice, including augmented MDSC recruitment, increased levels of ROS and p-Stat3 in MDSCs, and higher suppressive function of MDSCs in T-cell proliferation, which were abrogated by calcitriol supplementation. On the basis of our results, we concluded that calcitriol abrogated the IL6-induced aggressive tumor behavior and MDSC recruitment to inhibit esophageal tumor promotion. Therefore, we suggest that supplementation with vitamin D 3 may be a promising strategy for the prevention and treatment of esophageal SCC.

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Section: Discussionmentioning

confidence: 99%

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

Chen

Hsieh

et al. 2015

Molecular Cancer Therapeutics

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“…the addition of BH3-only proteins (Guscetti et al, 2005) or the comparative exploration of the effects of specific compounds on interactions between Bcl-2 family members of canine versus human origin (Silva et al, 2011) thus further assessing the potential value of the canine model. Several murine models, in particular genetically engineered mouse models, have proven invaluable for mechanistic and drug discovery studies (Cheon and Orsulic, 2011;Ruggeri et al, 2014). As a specific example, the Eµ-myc lymphoma model has been successfully used to model the efficacy of the Bcl-2 antagonist ABT-737 against an aggressive lymphoma subtype (Mason et al, 2008), and its derivative ABT-199 is currently tested in phase II and III studies (Besbes et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…They have evolved in recent years to a vast array of sophisticated models that are continuously broadening and deepening our knowledge of cancer biology (Cheon and Orsulic, 2011;Ruggeri et al, 2014). A number of limitations in the use of mice, however, have become apparent in recent years.…”

Section: Introductionmentioning

confidence: 99%

Sequence and partial functional analysis of canine Bcl-2 family proteins

Brot

Schade

Croci

et al. 2016

Research in Veterinary Science

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Dogs present with spontaneous neoplasms biologically similar to human cancers. Apoptotic pathways are deregulated during cancer genesis and progression and are important for therapy.We have assessed the degree of conservation of a set of canine Bcl-2 family members with the human and murine orthologs. To this end, seven complete canine open reading frames were cloned in this family, four of which are novel for the dog, their sequences were analyzed, and their functional interactions were studied in yeasts. We found a high degree of overall and domain sequence homology between canine and human proteins. It was slightly higher than between murine and human proteins. Functional interactions between canine pro-apoptotic Bax and Bak and anti-apoptotic Bcl-xL, Bcl-w, and Mcl-1 were recapitulated in yeasts. Our data provide support for the notion that systems based on canine-derived proteins might faithfully reproduce Bcl-2 family member interactions known from other species and establish the yeast as a useful tool for functional studies.

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“…We recognize that each different type of animal cancer model has intrinsic advantages and limitations and that no single model can capture all the different aspects of tumor growth characteristics and treatment approaches. Rather, they should be viewed as a portfolio of sophisticated biologic tools that can be used optimally in the drug discovery process to answer specific experimental questions (39,40). Accordingly, in this article, we have studied the antitumor efficacy of the new G4 compound EMICORON on different preclinical models of colon cancer that may mimic the clinical situation.…”

Section: Discussionmentioning

confidence: 99%

Targeting G-Quadruplex DNA Structures by EMICORON Has a Strong Antitumor Efficacy against Advanced Models of Human Colon Cancer

Porru¹,

Artuso²,

Salvati³

et al. 2015

Molecular Cancer Therapeutics

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We previously identified EMICORON as a novel G-quadruplex (G4) ligand showing high selectivity for G4 structures over the duplex DNA, causing telomere damage and inhibition of cell proliferation in transformed and tumor cells. Here, we evaluated the antitumoral effect of EMICORON on advanced models of human colon cancer that could adequately predict human clinical outcomes. Our results showed that EMICORON was well tolerated in mice, as no adverse effects were reported, and a low ratio of sensitivity across human and mouse bone marrow cells was observed, indicating a good potential for reaching similar blood levels in humans. Moreover, EMICORON showed a marked therapeutic efficacy, as it inhibited the growth of patient-derived xenografts (PDX) and orthotopic colon cancer and strongly reduced the dissemination of tumor cells to lymph nodes, intestine, stomach, and liver. Finally, activation of DNA damage and impairment of proliferation and angiogenesis are proved to be key determinants of EMICORON antitumoral activity. Altogether, our results, performed on advanced experimental models of human colon cancer that bridge the translational gap between preclinical and clinical studies, demonstrated that EMICORON had an unprecedented antitumor activity warranting further studies of EMI-CORON-based combination treatments.

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Animal models of disease: Pre-clinical animal models of cancer and their applications and utility in drug discovery

Cited by 290 publications

References 84 publications

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

Sequence and partial functional analysis of canine Bcl-2 family proteins

Targeting G-Quadruplex DNA Structures by EMICORON Has a Strong Antitumor Efficacy against Advanced Models of Human Colon Cancer

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