Mouse Models in Prostate Cancer Translational Research: From Xenograft to PDX

Rea, Domenica; Vecchio, Vitale Del; Palma, Giuseppe; Barbieri, Antônio; Falco, Michela; Luciano, Antonio; Biase, Davide De; Perdonà, Sisto; Facchini, Gaetano; Arra, Claudio

doi:10.1155/2016/9750795

Cited by 45 publications

(39 citation statements)

References 96 publications

(100 reference statements)

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“…A burgeoning body of evidence has demonstrated that miRNAs serve a crucial role in a variety of biological processes, including cell growth (6), cell apoptosis (7) and development of the nervous system (8). In oncological studies, a growing number of miRNAs have been confirmed to have an association with a large number of neoplasms (9–11). For example, miR-15a and miR-16 may be closely associated with cancer pathogenesis (12,13).…”

Section: Introductionmentioning

confidence: 99%

The diagnostic effect of serum miR-196b as biomarker in colorectal cancer

2016

Biomedical Reports

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The microRNA, miR-196b, serves a role in normal cell differentiation, proliferation and tumorigenesis of different types of cancer. The aim of the present study was to explore the serum expression of miR-196b in colorectal cancer (CRC) and its correlation with clinicopathological features. Sera samples were obtained from 103 patients with CRC, 51 patients with colorectal adenoma (Ad) and 100 healthy individuals for the present study. The serum expression of miR-196b in sera samples of the three cohorts was detected using reverse transcription-quantitative polymerase chain reaction. The diagnostic value of miR-196b in the serum of the patients with CRC was evaluated by receiver operating characteristic (ROC) curve and survival analysis, using the Kaplan-Meier method, which was performed with the data from a 5-year follow-up. The expression of miR-196b in the serum of patients with CRC was significantly higher compared with that in Ad patients or healthy individuals (all P<0.001), and the overexpression of serum miR-196b was clearly associated with lymph node invasion, differentiation, and the tumor-lymph nodes-metastasis stage (all P<0.05). ROC curve analysis demonstrated that, comparing patients with CRC with healthy individuals, the area under the curve of serum miR-196b was 0.8135, and its specificity and sensitivity were 63 and 87.38%, respectively, at a diagnostic threshold of −4.785. Patients with CRC of miR-196b-high status had shorter overall survival and disease-free survival rates compared with those of miR-196b-low status. In conclusion, the results of the present study demonstrated that serum miR-196b is upregulated in CRC, and may have an application as a diagnostic and prognostic biomarker for patients with CRC.

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Section: Introductionmentioning

confidence: 99%

The diagnostic effect of serum miR-196b as biomarker in colorectal cancer

2016

Biomedical Reports

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“…We used mouse PCa cell lines since human PCa cell lines do not propagate easily in xenograft mouse models. 35 The average weight of mice was maintained within a normal range during the study of both xenografted cell lines, indicating that ST1926 treatment was well tolerated ( Figure 7A). Treatment with ST1926 resulted in significant inhibition of tumor progression in PLum-AD and PLum-AI ( Figure 7B) injected mice.…”

Section: St1926 Inhibits Prostate Tumor Growth In Vivomentioning

confidence: 82%

“…We assessed the potential effect of ST1926 on tumor growth in vivo, we injected NOD‐SCID mice with PLum‐AD and PLum‐AI cells subcutaneously to generate PCa xenografts. We used mouse PCa cell lines since human PCa cell lines do not propagate easily in xenograft mouse models . The average weight of mice was maintained within a normal range during the study of both xenografted cell lines, indicating that ST1926 treatment was well tolerated (Figure A).…”

Section: Resultsmentioning

confidence: 99%

The synthetic retinoid ST1926 attenuates prostate cancer growth and potentially targets prostate cancer stem‐like cells

Bahmad

Samman

Monzer

et al. 2019

Molecular Carcinogenesis

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Retinoids are vitamin A derivatives that regulate crucial biological processes such as cellular proliferation, apoptosis, and differentiation. The use of natural retinoids in cancer therapy is limited due to their toxicity and the acquired resistance by cancer cells. Therefore, synthetic retinoids were developed, such as the atypical adamantyl retinoid ST1926 that provides enhanced bioavailability and reduced toxicity. We have assessed the in vitro and in vivo antitumor properties and mechanism of action of ST1926 in targeting cancer stem‐like cells population of human prostate cancer (PCa) cell lines, DU145 and PC3, and mouse PCa cell lines, PLum‐AD and PLum‐AI. We demonstrated that ST1926 substantially reduced proliferation of PCa cells and induced cell cycle arrest, p53‐independent apoptosis, and early DNA damage. It also decreased migration and invasion of PCa cells and significantly reduced prostate spheres formation ability in vitro denoting sufficient eradication of the self‐renewal ability of the highly androgen‐resistant cancer stem cells. Importantly, ST1926 potently inhibited PCa tumor growth and progression in vivo. Our results highlight the potential of ST1926 in PCa therapy and warrant its clinical development.

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“…Mouse models of cancer are classified into four groups: i) GEM models; ii) cell line xenografts; iii) patient-derived xenografts (PDXs), and iv) syngeneic models (Rea et al, 2016). Prostate cancer GEM models are further divided into four different groups: i) transgenic; ii) whole-body knockouts; iii) conditional knockouts and; iv) gain-of-function models (Grabowska et al, 2014;Valkenburg & Williams, 2011).…”

Section: Mouse Models Of Prostate Cancermentioning

confidence: 99%

Overview of Genetically Engineered Mouse Models of Prostate Cancer and Their Applications in Drug Discovery

2018

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Prostate cancer (PCa) is the most common malignant visceral neoplasm in males in Western countries. Despite progress made in the early treatment of localized malignancies, there remains a need for therapies effective against advanced forms of the disease. Genetically engineered mouse (GEM) models are valuable tools for addressing this issue, particularly in defining the cellular and molecular mechanisms responsible for tumor initiation and progression. While cell and tissue culture systems are important models for this purpose as well, they cannot recapitulate the complex interactions within heterotypic cells and the tumor microenvironment that are crucial in the initiation and progression of prostate tumors. Limitations of GEM models include resistance to developing invasive and metastatic tumors that resemble the advanced stages of human PCa. Nonetheless, because genetic models provide valuable information on the human condition that would otherwise be impossible to obtain, they are increasingly employed to identify molecular targets and to examine the efficacy of cancer therapeutics. The aim of this overview is to provide a brief but comprehensive summary of GEM models for PCa, with particular emphasis on the strengths and weaknesses of this experimental approach. © 2018 by John Wiley & Sons, Inc.

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Mouse Models in Prostate Cancer Translational Research: From Xenograft to PDX

Cited by 45 publications

References 96 publications

The diagnostic effect of serum miR-196b as biomarker in colorectal cancer

The diagnostic effect of serum miR-196b as biomarker in colorectal cancer

The synthetic retinoid ST1926 attenuates prostate cancer growth and potentially targets prostate cancer stem‐like cells

Overview of Genetically Engineered Mouse Models of Prostate Cancer and Their Applications in Drug Discovery

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