Animal models of medullary thyroid cancer: state of the art and view to the future

Mantovani, Giovanna; Gaudenzi, Germano; Circelli, Luisa; Manzoni, M.; Bassi, Andrea; Fioritti, Niccolò; Faggiano, Antongiulio; Colao, Annamaria

doi:10.1530/erc-16-0399

Cited by 30 publications

(20 citation statements)

References 79 publications

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“…In addition, this approach will provide insight into early stages of medullary thyroid carcinoma. These studies would complement published work on animal models of medullary thyroid tumors that largely rely on global, non-selective, or non-inducible gene activation/inactivation in the thyroid (21).…”

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confidence: 85%

Selective Ablation of Tumor Suppressors in Parafollicular C Cells Elicits Medullary Thyroid Carcinoma

Song

Lin

Yao

et al. 2017

Journal of Biological Chemistry

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Among the four different types of thyroid cancer, treatment of medullary thyroid carcinoma poses a major challenge because of its propensity of early metastasis. To further investigate the molecular mechanisms of medullary thyroid carcinoma and discover candidates for targeted therapies, we developed a new mouse model of medullary thyroid carcinoma based on our mouse line. This system enables gene manipulation in parafollicular C cells in the thyroid, the purported cells of origin of medullary thyroid carcinoma. Selective inactivation of tumor suppressors, such as, , and, in mature parafollicular C cells via an inducible Cre recombinase from led to development of murine medullary thyroid carcinoma. Loss of accelerated /-induced medullary thyroid carcinoma, indicating interactions between pathways controlled by tumor suppressors. Moreover, labeling differentiated parafollicular C cells by allows us to follow their fate during malignant transformation to medullary thyroid tumor. Our findings support a model in which mutational events in differentiated parafollicular C cells result in medullary thyroid carcinoma. Through expression analysis including RNA-Seq, we uncovered major signaling pathways and networks that are perturbed following the removal of tumor suppressors. Taken together, these studies not only increase our molecular understanding of medullary thyroid carcinoma but also offer new candidates for designing targeted therapies or other treatment modalities.

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mentioning

confidence: 85%

Selective Ablation of Tumor Suppressors in Parafollicular C Cells Elicits Medullary Thyroid Carcinoma

Song

Lin

Yao

et al. 2017

Journal of Biological Chemistry

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“…On these bases and according to the obtained data, targeting tumor-related receptors could represent a successful drug delivery strategy against tumors. Additional in vivo studies are needed to better investigate the efficiency and specificity of these new delivery systems, and we would have benefit of transparent in vivo models, such as zebrafish embryos, to evaluate fluorescent-labeled liposome biodistribution [47][48][49][50][51].…”

Section: Discussionmentioning

confidence: 99%

Urotensin-II-Targeted Liposomes as a New Drug Delivery System towards Prostate and Colon Cancer Cells

Zappavigna

Abate

Cossu

et al. 2019

Journal of Oncology

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Urotensin-II (UT-II) and its receptor (UTR) are involved in the occurrence of different epithelial cancers. In particular, UTR was found overexpressed on colon, bladder, and prostate cancer cells. The conjugation of ligands, able to specifically bind receptors that are overexpressed on cancer cells, to liposome surface represents an efficient active targeting strategy to enhance selectivity and efficiency of drug delivery systems. The aim of this study was to develop liposomes conjugated with UT-II (LipoUT) for efficient targeting of cancer cells that overexpress UTR. The liposomes had a mean diameter between 150 nm and 160 nm with a narrow size distribution (PI≤0.1) and a doxo encapsulation efficiency of 96%. Moreover, the conjugation of UT-II to liposomes weakly reduced the zeta potential. We evaluated UTR expression on prostate (DU145, PC3, and LNCaP) and colon (WIDR and LoVo) cancer cells by FACS and western blotting analysis. UTR protein was expressed in all the tested cell lines; the level of expression was higher in WIDR, PC3, and LNCaP cells compared with LoVo and DU145. MTT cell viability assay showed that LipoUT-doxo was more active than Lipo-doxo on the growth inhibition of cells that overexpressed UTR (PC3, LNCaP, and WIDR) while in LoVo and DU145 cell lines, the activity was similar to or lower than that one of Lipo-doxo, respectively. Moreover, we found that cell uptake of Bodipy-labeled liposomes in PC3 and DU145 was higher for LipoUT than the not-armed counterparts but at higher extent in UTR overexpressing PC3 cells (about 2-fold higher), as evaluated by both confocal and FACS. In conclusion, the encapsulation of doxo in UT-II-targeted liposomes potentiated its delivery in UTR-overexpressing cells and could represent a new tool for the targeting of prostate and colon cancer.

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“…A thyroid cancer model using Drosophila genetically mutated for the development of molecular targeted drugs contributed to the identification of candidate compounds. 40,47) Vandetanib was approved by the U.S. Food and Drug Administration and became one of the chemotherapeutic agents used to treat patients with thyroid cancer. 48) Therefore, human disease models using insects can contribute to drug discovery for cancer therapy.…”

Section: Identification Of Drug Candidates Using Insect Disease Modelsmentioning

confidence: 99%

Facilitating Drug Discovery in Human Disease Models Using Insects

Matsumoto

2020

Biological & Pharmaceutical Bulletin

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Drugs are developed through basic studies and clinical trials. In basic studies, researchers seek drug candidates using in vitro evaluation systems and subsequently examine their effectiveness in animal experiments as in vivo evaluations. Drug candidates identified in basic studies are tested to determine whether they are effective against human diseases in clinical trials. However, most drug candidates identified in in vitro evaluation systems do not show therapeutic effects in animal experiments due to pharmacokinetics and toxicity problems in the in vivo evaluations. This review outlines drug discovery using insect disease models that allow us to perform in vivo screening. Since insects have various advantages as experimental animals such as low cost for rearing and few ethical concerns, researchers can perform large-scale in vivo screening to find drug candidates. Silkworms are insects frequently used for studies of drug efficacy, pharmacokinetics, and toxicity. Based on silkworm research, I describe the benefits of using insect disease models for drug discovery. The use of insect disease models for in vivo screening is expected to facilitate drug discovery.

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Animal models of medullary thyroid cancer: state of the art and view to the future

Cited by 30 publications

References 79 publications

Selective Ablation of Tumor Suppressors in Parafollicular C Cells Elicits Medullary Thyroid Carcinoma

Selective Ablation of Tumor Suppressors in Parafollicular C Cells Elicits Medullary Thyroid Carcinoma

Urotensin-II-Targeted Liposomes as a New Drug Delivery System towards Prostate and Colon Cancer Cells

Facilitating Drug Discovery in Human Disease Models Using Insects

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